Journal of Life Science and Biomedicine  
J Life Sci Biomed, 10 (6): 70-79, 2020  
ISSN 2251-9939  
Recent drugs and vaccine candidates to tackle  
Ehsan GHARIB MOMBENI , Mahshad YOUSEFI2, Saeid CHEKANI-AZAR3, Mohamed Samy ABOUSENNA4,  
Kosar ARMIN2, Fatemeh SHAVANDI2, Elham EMAMI5 and Yadollah BAHRAMI6  
1PhD, Department of Pathobiology, Shahid Chamran University of Ahvaz, Iran  
2MD, Hamadan University of Medical Sciences, Hamadan, Iran  
3PhD, Faculty of Veterinary Medicine, Animal Physiology, Atatürk University, Turkey  
4PhD of Virology, Central Laboratory for Evaluation of Veterinary Biologics, Cairo, Egypt  
5PhD, Assistant prof., Department of Pediatric, Shahrekord University of Medical Science, Shahrekord, Iran  
6PhD of Animal Biotechnology, Young Researchers Elite Club, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran  
Corresponding author’s Email:;  
Review Article  
PII: S225199392000009-10  
Introduction. The global devastating pandemic coronavirus disease 2019 (COVID-  
19) is a worldwide multisystemic infection caused by the novel severe acute  
respiratory syndrome coronavirus 2 (SARS-CoV-2), which has emerged as a  
menace to the global public health and countries economy. There is a crucial  
necessity for the suggestion of effective drugs to eliminate the virus outbreak.  
Several candidate drugs with existing emerging evidence try to offer a  
pharmacological strategy that may inhibit infection in COVID-19 patients. By,  
October 2020, scientists have nominated some reliable and safe types of  
coronavirus vaccines like Pfizer, Moderna, AstraZeneca, CureVac, CoronaVac, etc.  
that are effective and showed 95% to 90% protection, respectively. Aim. This  
review highlights important clinical and in vitro studies, uses of potent antiviral  
drugs and most recent vaccines against COVID-19 disease.  
Rec. 02 September 2020  
Rev. 18 November 2020  
Pub. 25 November 2020  
Actemra, Antiviral medicines,  
ARCoV, AstraZeneca,  
ChulaCov19, CoronaVac,  
COVID-19, CureVac, CytoSorb,  
Ivermectin, Moderna,  
Oleandrin, Pfizer, Remdesivir,  
Ritonavir, Vaccines.  
Novel coronavirus (2019-nCoV) likes other coronaviruses belong to the coronaviridae family. Coronaviruses (CoVs)  
belong to the genus Coronavirus in the Coronaviridae family [1]. The CoVs are enveloped with a crown-like  
appearance with 120-160 nm in diameter, single-stranded RNA viruses between 27 kb and 31.5 kb with positive  
polarity, which the largest among known RNA viruses [2, 3]. Members of the subfamily Coronavirinae are  
comprised of four genera. The genus Alphacoronavirus contains human and many animal viruses. The genus  
Betacoronavirus includes the Severe Acute Respiratory Syndrome-related (SARS-related) coronavirus, Middle  
Eastern Respiratory Syndrome (MERS) coronavirus, together with a number of human and animal  
coronaviruses. The genus Gammacoronavirus contains viruses of cetaceans (whales) and birds, and the genus  
Deltacoronavirus contains viruses isolated from pigs and birds. It seems that alpha- and beta-coronaviruses  
apparently originate from mammals, in particular from bats. The gamma- and delta-viruses originate from pigs  
and birds. Although alpha-coronaviruses cause a mild infection, apparently the beta-coronaviruses cause severe  
disease and fatalities in humans [4, 5].  
On 31 December 2019, a number of patients with signs of pneumonia and without any specified etiology  
were reported in Wuhan, Hubei Province China. On 9 January 2020, China Centers for Disease Control and  
Prevention (CDC) confirmed that the cause of the outbreak is a novel coronavirus. In addition, it reported that  
based on phylogeny it belongs to the SARS-CoV clade [6]. By December 27, 2020, there has been over 80 million  
people infected and 1,761,749 deaths (Centre for Systems Science and Engineering. COVID-19 dashboard, 2020;  
Available from: The major response to the coronavirus disease 2019  
(COVID-19; previously 2019-nCoV) outbreak has been largely limited to monitoring/containment around the  
world. Meanwhile, there are many scientists looking for an effective solution to eliminating the COVID-19. In  
the following, there are some valid recent vaccines and effective medicines to tackle the novel coronavirus.  
Citation: Gharib Mombeni E, Yousefi M, Chekani-Azar S, Abousenna MS, Armin K, Shavandi F, Emami E and Bahrami Y. Recent drugs and vaccines candidates  
Routinely, the approbation of an effective vaccine requires years of research and in vivo and in vitro examination  
before reaching the countries. Vaccine investigation procedures began in January 2020 with the deciphering of  
the SARS-CoV-2 genome. The first vaccine safety trials in humans started in March, and in October 2020, 10  
reached the final stages of testing. However, a few vaccines have succeeded in stimulating the immune system  
to produce effective antibodies against the virus. By, October 2020, researchers tested 48 vaccines in clinical  
trials on humans, and at least 89 preclinical vaccines were under active investigation in animals. However,  
scientists have nominated some reliable types of vaccines effective on coronavirus this year [7].  
1. Moderna vaccine. Moderna vaccine (produced by the collaboration of the National Institute of Allergy  
and Infectious Diseases (NIAID) and US biotech company) is based on messenger RNA mRNA-1273) encodes the  
spike 2 protein (S-2P) antigen, consisting of the SARS-CoV-2 glycoprotein with a transmembrane anchor and an  
intact S1S2 cleavage site. S-2P is stabilized in its prefusion conformation by two consecutive proline  
substitutions at amino acid positions 986 and 987, at the top of the central helix in the S2 subunit [8], which  
triggers the body's immune system by producing viral spikes and spike protein fragments in the patient cells  
and on the cells surface, where the immune system could recognize, when a vaccinated cell dies, the cell debris  
will contain many spike proteins and protein fragments, the antigen-presenting cell will recognize it, on the  
other hand the T helper cells will detect the spike protein fragments on the cell surface which are essential to  
initiate the cellular and humoral immunity pathways to combat the SARS-CoV-2 infection. At the beginning of  
developing the vaccine, they reported the vaccine protects non-human primates (monkeys) against the SARS-  
CoV-2. In March, the company put the first COVID-19 vaccine into human trials, which had successful results.  
The vaccine testing began on July 27. The US biotech company Moderna after a trial enrolled 30,000  
participants included white, non-white, black, and Latina with a wide range of age (over and under 65 years old)  
around the United States (89 sites) reported its trial showed 94.5% effectiveness [7, 9] and trial-limiting safety  
concerns were identified [10].  
2. Pfizer vaccine. The German company BioNTech collaborates with Pfizer, which is based in New York,  
and the Chinese drugmaker Fosun Pharma to produce mRNA vaccine (BNT162b2) that encodes a prefusion  
stabilized, membrane-anchored SARS-CoV-2 full-length spike protein [11]. After a trial in May 2020, they found  
that the vaccine (BNT162b2) caused volunteers to produce antibodies against SARS-CoV-2, as well as T cells  
against the virus. They found that the vaccine had not any side effects, such as fevers and fatigue. On July 27,  
the companies designed a trial with more than 30,000 volunteers in Argentina, Brazil, Germany, and the United  
States [7, 9]. The Pfizer company announced that the vaccine was more than 90% effective [12]. Comparable with  
Moderna’s vaccine, Pfizer and BioNTech’s is an mRNA-based vaccine, both BNT and mRNA-1273 require booster  
doses in order to ensure high neutralizing antibody titer and (presumably) long term immunogenicity. Despite  
the necessity of a second dose, the antibody response against the SARS-CoV-2 receptor-binding domain (RBD)  
of both vaccines showed significantly higher titers compared to patients who have recovered from COVID-19  
[13, 14] both vaccines require to be kept in a deep freeze condition. Consequently, the Pfizer vaccine will have to  
be frozen to minus 80 degrees Celsius (minus 112 degrees Fahrenheit) until the injection time [7, 9]., while  
Moderna’s vaccine could be stored and shipped at minus 20 degrees Celsius (stable up to six months) ,  
anticipated to persist stably at a refrigerator temperature (2° to 8°C = 36° to 46°F) for 30 days and at a room  
temperature remain stable for up to 12 hours (  
3. CureVac. CureVac is a biopharmaceutical company, based in the Netherlands and headquartered in  
Tübingen, Germany. In March, CureVac began its research on an mRNA vaccine. The company reported  
promising responses in mice. CureVac announced that the company would make the vaccine by the end of 2020  
and hoped to gain human usage approval in 2021 [7, 15, 16].  
4. The US company Arcturus Therapeutics and Duke-NUS Medical School in Singapore produced a self-  
replicating mRNA-based vaccine which leads to greater production of viral proteins [7].  
5. Imperial College London researchers have produced an RNA-based vaccine that has a self-amplifying  
method, which boosts the production of a viral protein to trigger the immune system. On June 15, they began  
the trials; the researchers announced the vaccine might be ready for human usage by the end of 2020 [7].  
6. ARCoV. In June, Chinese Military Medical researchers, Suzhou Abogen Biosciences and Walvax  
Biotechnology announced that they began a trial on an mRNA-based vaccine (ARCoV) [7, 17].  
Citation: Gharib Mombeni E, Yousefi M, Chekani-Azar S, Abousenna MS, Armin K, Shavandi F, Emami E and Bahrami Y. Recent drugs and vaccines candidates  
7. ChulaCov19. On Sept. 29, Thailand’s Chulalongkorn University announced that they are developing an  
mRNA-based vaccine (ChulaCov19) [7].  
8. Entos is a Canadian pharmaceutical company that created a DNA vaccine (Covigenix VAX-001) for the  
coronavirus. Entos instead of spike protein gene chose the gene for nucleocapsid, a protein that sits inside the  
virus’s envelope [7, 18].  
9. Sanofi is a French pharmaceutical company that corporate with Translate Bio. The company  
announced an mRNA vaccine that produces an acceptable level of antibody in mice and monkeys trials [7, 19-21].  
10. On June 30, the Japanese biotechnology company AnGes with corporate by Osaka University and  
Takara Bio started a trial on a DNA-based vaccine. The vaccine was created based on a consensus SARS-CoV-2  
spike glycoprotein sequence with an N-terminal IgE leader, added to enhance expression in target cells and  
increase immunogenicity .The company is planning to produce the vaccine by the end of 2020 [7, 22, 23].  
11. Zydus. In July, Zydus Cadila an Indian pharmaceutical company began testing a DNA-based skin-patch  
vaccine [7].  
12. The US company Inovio produced a DNA-based vaccine that applied to the skin with electric pulses  
from a hand-held device. They announced that there are not any side-effects. On Sept. 28, the F.D.A. hold the  
research due to needing the delivery device [7, 24].  
13. In June, The Korean company Genexine began producing a DNA-based vaccine [7, 25].  
14. CoronaVac. CoronaVac (Sinovac Life Sciences, Beijing, China) is an inactivated vaccine against SARS-  
CoV-2 which was developed from a SARS-CoV-2 strain isolated from a patient in the Jinyintan Hospital, Wuhan.  
The virus was propagated on Vero cell line, and it was inactivated with β-propiolactone, the prepared antigen  
then adsorbed onto an adjuvant (aluminum hydroxide) [26] .CoronaVac induced humoral immune responses  
against SARS-CoV-2, which supported the approval of emergency use of CoronaVac in China and other different  
countries., there is no clear evidence that the vaccine induced T-cell responses [27].  
15. AstraZeneca. It is recombinant vaccine (ChAdOx1) which was developed at Oxford University, The  
ChAdOx1 nCoV-19 vaccine (AZD1222) consists of a replication-deficient chimpanzee adenoviral vector ChAdOx1,  
containing the SARS-CoV-2 structural surface glycoprotein antigen (spike protein; nCoV-19) gene that  
expresses a full S protein it was found that the recombinant vaccine ChAdOx1 has accepted safety profile well  
tolerated and immunogenic [28, 29].  
Actemra (tocilizumab), a Roche’s anti-inflammatory drug  
In numerous patients, COVID-19 infection is associated with a cytokine storm [30-35]. In this case,  
coronavirus patients will encounter serious lung complications and it can also lead to death and in recovered  
cases, the excessive immune responses lead to long-term lung damage and fibrosis [36, 37]. Nevertheless, there  
is no applicable specific antiviral treatment, and or designing potent antiviral drugs against the COVID-19 will  
take years to develop [38-40], use of anti-inflammatory drugs like Actemra can be more effective, to tackle the  
COVID-19 outbreak. Perrone et al. [41] reported that Tocilizumab reduced lethality rate at 30 days compared  
with the null hypothesis, without significant toxicity, which supports the use of Tocilizumab among patients  
not requiring mechanical ventilation and independent of the effect of corticosteroids.  
China approved the use of Roche’s anti-inflammatory drug Tocilizumab (trade names: Actemra, RoActemra)  
an interleukin-6 inhibitor [42]to treat patients infected with the new coronavirus who have developed  
serious lung damage and also have elevated levels of IL-6 a biomarker for inflammation and a high-level  
immune responsein the blood that is associated with a higher mortality rate in people with community-  
Actemra has known as interleukin-6 inhibitor can interrupt Cytokine Release Syndrome and regulate systemic  
inflammatory response and complication of some diseases or infections [43].  
Favipiravir (T-705), a broad-spectrum inhibitor of viral RNA polymerase [44] and ribavirin  
Favipiravir and ribavirin are representative of nucleoside analogs. Nucleoside analogs as a broad-spectrum  
antiviral have several mechanisms of effects in vitro, including lethal mutagenesis, non-specific the nascent  
DNA chain termination, and inhibiting the biosynthesis of nucleotides. Wang et al. [45] proved that favipiravir  
combined with oseltamivir is more effective than oseltamivir alone in treating severe influenza (RNA virus).  
Coronaviruses are RNA viruses. However, they express exonuclease in non-structural protein 14 (nsp14-ExoN)  
Citation: Gharib Mombeni E, Yousefi M, Chekani-Azar S, Abousenna MS, Armin K, Shavandi F, Emami E and Bahrami Y. Recent drugs and vaccines candidates  
and are conserved throughout the coronavirus family, which has an RNA proofreading function [46]. Smith et  
al. [47] reported that ribavirin in an in vitro experiment has a low effect on coronavirus. In 2017 Furuta et al. [44]  
reported an effective inhibitor of viral RNA polymerase (Favipiravir, T-705; 6-fluoro-3-hydroxy-2-pyrazine  
carboxamide) as an anti-viral medicine that selectively and potently inhibits the RNA-dependent RNA  
polymerase (RdRp) of RNA viruses. It was discovered through a screening chemical library for anti-viral activity  
against the influenza virus by Toyama Chemical Co., Ltd. Favipiravir undergoes a phosphoribosylation in the  
hostess cell to be an active form, favipiravir-RTP (favipiravir ribofuranosyl-5-triphosphate), which is recognized  
as a substrate by RdRp, and inhibits the RNA polymerase activity. Since the catalytic domain of RdRp is  
preserved among numerous types of RNA viruses, this mechanism of action underpins a broader spectrum of  
anti-viral activities of favipiravir. Favipiravir is effective against a wide range of types and subtypes of influenza  
viruses, including to anti-influenza drugs resistant strains. Noticeably, favipiravir has potent anti-viral  
activities against other RNA viruses, likewise; arenaviruses, bunyaviruses, and filoviruses, all of which are known  
to cause fatal hemorrhagic fever. These unique anti-viral profiles will make favipiravir a potentially promising  
drug for specifically incurable RNA viral infections.  
Ivermectin, an inhibitor of the replication of SARS-CoV-2 in vitro  
Ivermectin is an effective inhibitor of the SARS-CoV-2 clinical isolate Australia/VIC01/2020. Ivermectin has  
been licensed for more than 20 years for the treatment of parasitic infections in human and animals.  
Considering that this well-tolerated drug, Mastrangelo et al. [48] in 2102, reported new prospects for an old  
widely used anti-helminthic medicine, Ivermectin, as a potent inhibitor of flavivirus replication specifically  
targeting NS3 (non-structural protein 3) helicase domain activity. This drug not only displayed a high-predicted  
binding affinity towards the modeled NS3 ssRNA binding pocket but also inhibited the NS3 helicase activity of  
different flaviviruses in vitro at sub-micromoles concentrations. Most importantly, ivermectin proved to be a  
selective inhibitor of the replication of several flaviviruses in cell culture, such as Japanese encephalitis (JEV),  
tick-borne encephalitis viruses (TBEV), and dengue viruses (DENV) (sub-micromolar EC50 values) [49], and a  
highly potent inhibitor of yellow fever virus (YFV) replication (sub-nanomolar EC50 values) [49]. Caly et al. [50]  
in 2020 also reported Ivermectin as an FDA-approved anti-parasitic, is an inhibitor of the causative virus  
(SARS-CoV-2), with a single addition to Vero-hSLAM cells 2 hours post-infection with SARS-CoV-2 able to effect  
5000-fold reduction in viral RNA at 48 h. Therefore, this drug warrants further investigation for possible  
benefits in humans, especially against the virus COVID-19.  
Remdesivir (GS-5734)  
Remdesivir is an adenosine analog, which interferes with the activity of viral RNA-dependent RNA-  
polymerases (RdRp) and results in premature termination, which is effective against a wide range of RNA  
viruses (including SARS/MERS-CoV) [51, 52]. The chloroquine is used against malarial, autoimmune disease, and  
recently introduced as a potential broad-spectrum antiviral medicine. The function of chloroquine is to increase  
endosomal pH, which requires virus/cell fusion, as well as it interferes with the glycosylation of cellular  
receptors of SARS-CoV [53-55]. The results of in vitro cell with submicromolar EC50 values confirmed that  
remdesivir has potent antiviral activity in vitro against human coronaviruses (HCoV-OC43 and HCoV-229E)  
and coronaviruses related to zoonotic bat-CoV [56]. Jordan et al. (2018) reported that GS-5734 triphosphate  
might not able to excised by the proofreading activity of nsp14 due to lack of immediate chain termination, as  
observed in human respiratory syncytial virus (RSV) polymerase [57, 58].  
Ibavirin, penciclovir, nitazoxanide, nafamostat, chloroquine  
Wang et al. [45] evaluated five antiviral medications including ribavirin, penciclovir, nitazoxanide,  
nafamostat, chloroquine, and two broad-spectrum antiviral medicines remdesivir (GS5734) and favipiravir (T-  
705) against a clinical isolate of 2019- nCoV in vitro. Hence, their evaluation was based on measuring the effects  
of these agents on the cytotoxicity, virus yield, and infection rates of 2019-nCoVs in the Vero E6 cells, which had  
infected with nCoV2019BetaCoV/Wuhan/WIV04/2019. They reported that high concentrations of three  
nucleoside analogs including ribavirin, penciclovir, and favipiravir were reduced the viral infection. Nafamostat,  
which has anti-membrane fusion activity, is a potent inhibitor against MERS-Cov and COVID-19. The  
nitazoxanide, which is an antiprotozoal medicine, has antiviral activity against animals and humans  
coronaviruses including COVID-19. Remdesivir and chloroquine potently blocked virus infection. Furthermore,  
chloroquine is a cheap and safe medicine that has an immune-modulating activity, which may improve its anti-  
Citation: Gharib Mombeni E, Yousefi M, Chekani-Azar S, Abousenna MS, Armin K, Shavandi F, Emami E and Bahrami Y. Recent drugs and vaccines candidates  
viral efficacy in the in vivo. In addition, oral administration of chloroquine can be prepared an efficient dosage  
in the lungs [59, 60].  
According to research, while ACE2 protects the lungs from injury, it is a key receptor for severe acute  
respiratory syndrome coronavirus (SARS-CoV). There is a report that injecting SARS-CoV spike into mice  
decreased ACE2 expression levels, thereby worsening lung injury [61, 62]. Recent studies stated that SARS-CoV-  
2 spike protein recognized human ACE2 even higher binding affinity than spike from SARS-CoV. ACE2 is in  
alveolar epithelial type 2 cells which produce surfactant that prevents alveoli from collapse, heart, kidney, blood  
vessels, and intestine that can explain the multi-organ dysfunction observed in patients. Scientists have created  
artificial ACE-2 proteins which might be able to act as decoys, luring the coronavirus away from vulnerable  
cells. Soluble recombinant human ACE2 (srhACE2) is a drug that has undergone phase 1 testing in healthy  
volunteers and phase 2 testing in some patients with acute respiratory distress syndrome (ARDS). Studies  
showed that this clinical-grade human ACE2 molecule can inhibit SARS-CoV-2 infection and reduce viral load  
and block entry of SARS-CoV-2 infection in host cells but the inhibition is not complete, although clearly dose-  
dependent [63-65]. Due to this fact, there might be a co-receptor or other mechanisms by which viruses can  
enter cells.  
Oleandrin extract derived from the Nerium oleander plant has shown inhibitory activity against several  
viruses such as HIV-1 and HTLV-1 [66]. Oleandrin is known as a toxic cardiac glycoside found in oleander, a  
poisonous plant, but research stated that it has a strong potential against envelope viruses. Hutchison et al. [67],  
has studied oleandrin’s potential in Southern Methodist University against leukemia virus type-1 so that  
inhibits human t-cell leukemia virus type-1 (HTLV-1) infectivity and env-dependent virological synapse  
formation. The results of use of this botanical glycoside demonstrated antiviral activity against enveloped  
viruses; therefore it can be an intriguing idea for researchers against the COVID-19 outbreak. Given that SARS-  
CoV-2 is also an enveloped virus, oleandrin could be effective in reducing viral load both when administered  
before and after infection. It can inhibit the Na, K-ATPase by blockade of ATP binding site. Another enzyme that  
requiring ATP is ACE2 which is an important receptor for SARS-CoV-2. An unpublished study has shown that  
sublingual administration of oleandrin caused more safe and rapid plasma concentration of oleandrin than oral  
administration because of the absence of the first passed effect of the liver. Oleandrin crosses the blood-brain  
barrier where can causes induction of some factors. According to poorly understood neurological manifestation  
presenting in some COVID-19 patients, oleandrin may have some benefit in preventing virus-associated  
neurological disease. Oleandrin can also make an anti-inflammatory response that prevents hyper-  
inflammatory responses to SARS-CoV-2. It can cause heart arrhythmias, making the plant dangerous to ingest.  
Scientists worry about the safety of oleandrin as a treatment for the coronavirus, given the toxicity of the plant.  
MK-4482 previously known as EIDD-2801, originally designed to fight the flu, is an orally bioavailable NHC  
prodrug that has a wide range of antiviral activity against SARS-CoV, MERS-CoV, and SARS-CoV-2 in primary  
HAE (human airway epithelial) cells [68]. The drug showed promising results against the new coronavirus in  
studies this spring in cells and on animals. It improves pulmonary function and virus titer drop and reduced the  
bodyweight loss. When NHC is incorporated during RNA synthesis, increase the mutation rates and leading to  
an error by inducing an error rate of replication that surpasses the error threshold allowed to sustain a virus  
Convalescent/Recovery plasma  
Plasma products of recovered patients are safe to use and can reduce the mortality of patients with severe  
influenza A and SARS-CoV infection and it is safe to use [69]. While Van Griensven et al. [70] with a non-  
randomized comparative study on Ebola virus infection showed that compared with patients in the treatment  
group, after infusion of up to 500 ml of plasma, has not seen any significant improvement in survival rate [70].  
The efficacy and safety of convalescent plasma for patients, which infected with COVID-19, should be evaluated  
by considering titers of plasma neutralizing antibodies in the donor rehabilitate patients.  
Citation: Gharib Mombeni E, Yousefi M, Chekani-Azar S, Abousenna MS, Armin K, Shavandi F, Emami E and Bahrami Y. Recent drugs and vaccines candidates  
Monoclonal antibody  
Mulangu et al. [71] conducted a prospective randomized controlled study on Ebola patients in the  
Democratic Republic of Congo. They reported that monoclonal antibody REGN-EB3 and monoclonal antibody  
114 (MAb114) significantly reduce the mortality rate [71].  
Lopinavir is a protease inhibitor (PI), which derived from ritonavir (antiretroviral medication). Co-  
administration of it with ritonavir showed potent and selective inhibitor activity against HIV-1 protease, which  
is an essential enzyme for the production of mature, infective viruses. Lopinavir with a modest antiviral activity  
against SARS-CoV-2 acts also against the viral 3CL protease [58]. Ritonavir increases drug bioavailability and its  
use together with Lopinavir and the immunomodulator interferon beta-1b is known for the treatment of MERS  
( number, NCT02845843) [72]. Prescription of lopinavir/ritonavir provides a sufficient and  
durable suppression of viral load uphold the CD4+ cell (cluster of differentiation 4) counts. In addition, reported  
that this regimen was more effective than nelfinavir in HIV-1-infected patients. The most common associated  
side effects were gastrointestinal disturbances, asthenia, headache, and skin rash [73]. Chan et al. [74] reported  
that lopinavir/ritonavir inhibited coronavirus replication to a certain extent in vitro experiments. Furthermore,  
they showed that the lopinavir/ritonavir and interferon-β1b in the treatment of marmoset infected with MERS-  
CoV as an animal model was convenient [74]. They reported that during the SARS epidemic in 2003, Hong Kong,  
China. 41 patients with SARS treated with the combination of lopinavir/ritonavir and ribavirin significantly  
showed acute respiratory distress syndrome or death lower than 111 SARS patients treated with ribavirin [75].  
Therefore, Lopinavir/ritonavir should be regarded as a candidate for an effective medicine in the management  
of COVID-19 infection. Beginning on January 18, 2020 and at a single hospital in Wuhan, China, Cao et al. [76]  
conducted an open-label randomized trial on 199 adult patients with COVID-19 infection to investigate the  
effectiveness of lopinavir-ritonavir for SARS-CoV-2. The patients also had pneumonia and oxygen saturation of  
<94% along with standard care alone (group 1) is compared to those receive 400 mg100 mg lopinavir-ritonavir  
orally and twice daily for a period of 14 days. They did not observe any significant difference between both  
groups however those who received lopinavir-ritonavir had lower 28-day mortality (19% vs. 25%, not  
significant). There are also no significant changes in coronavirus RNA concentrations obtained from throat  
swabs of both groups’ patients. Efficacy of chloroquine (CQ) has been tested in vivo using a mouse-adapted  
SARS-CoV (MA15) challenge to evaluate anti-viral efficacy which led to the hypothesis that the in vitro effects of  
CQ on MA15 and other coronaviruses was affecting entry and lipid membrane alterations, while in vivo the main  
effect was anti-inflammatory rather than anti-viral [77, 78]. This demonstrated that while there are features of  
infection that are altered by CQ treatment, it did not diminish viral replication in this model.  
Hydroxychloroquine (HCQ) and/or chloroquine (CQ)  
HCQ and CQ seem to demonstrate anti-viral properties in simple Vero cell assays. However, effects are not  
seen in life-like or more complex infection models such as organ-on-chips, which use human respiratory cells  
[78]. Based on some consistent findings observed in four different laboratories and also some evidence from  
related researches, Funnell et al. [78] reported no significant therapeutic benefit of HCQ in SARS-CoV-2  
infection model studies on non-human primates like hamsters. Thus, available data do not support the broad  
use of HCQ to treat COVID-19 disease.  
There are many guidelines for the treatment of patients with COVID-19 stating that glucocorticoids are  
either not recommended or contraindicated [79]; but in China, Zhao et al. [80] have a consensus on the use of  
corticosteroid in severe cases of 2019-nCoV pneumonia. Donnelly et al. [81] have identified the critical role of  
macrophage migration inhibitory factor (MIF) as inflammation-mediated lung injury in bronchoalveolar lavage  
fluids (BALF) from acute respiratory distress syndrome (ARDS) patients. The role of MIF as an inflammatory  
mediator and its complex with glucocorticoids is taken into consideration in recent and ongoing trials of  
glucocorticoids [82-88]. However, Fernandes et al. [82] stated that high doses of steroids may induce negative  
side effects due to the profound immunodepression and could counterbalance positive effects or could be even  
neutral or deleterious. Horby et al. [87] reported that glucocorticoids may regulate cytokine-mediated  
inflammation in the lung of COVID-19 patients and thereby reduce progression to respiratory failure and death.  
They stated significantly lower mortality at 28 days with a shorter duration of hospitalization in 10 days-  
Citation: Gharib Mombeni E, Yousefi M, Chekani-Azar S, Abousenna MS, Armin K, Shavandi F, Emami E and Bahrami Y. Recent drugs and vaccines candidates  
dexamethasone groups in comparison to the usual care group. Duration of hospitalization has a direct link with  
the risk of progression to invasive mechanical ventilation. However, they did not find any benefit among  
patients who were not receiving respiratory support at randomization and the results were consistent with  
possible harm in the dexamethasone group.  
CytoSorb® filter/device is a non-pyrogenic, sterile, single-use device placed in a blood pump circuit and it is  
containing adsorbent polymer beads designed to remove cytokines, as blood passes through the device.  
Cytosorbents® cytokine filter as a potential treatment methodology is used for the reduction of the cytokine  
storm and its pro-inflammatory levels and is of particular relevance as a bridge for therapy in patients with  
acute stage of COVID-19 [89]. Clinical experience suggests COVID -19 patients require higher anticoagulation at  
the start of treatment to prevent circuit clots off [89-92]. Anticoagulation in this case should be heparin [93]  
because this device may remove other anticoagulants and antiplatelet agents. Although, CytoSorb® reduce  
circulating inflammatory mediatory the risks are a hemodynamic compromise, arrhythmia, blood loss,  
hypoalbuminemia, thrombosis, air embolism, infection, hemolysis, hypocalcemia, thrombocytopenia, allergic  
reaction to device materials, unintended removal of other blood substances, risk related to vascular access  
placement, risk related to anticoagulation [89, 90, 93].  
Interferon beta-1a  
Interferons are molecules that are naturally produced by our cells in response to viruses. They can rouse  
the immune system to attack the invaders under the control of the body’s own tissues from any damage. The  
coronavirus appears to tamp down interferon so injecting synthetic interferons is now a standard treatment for  
a number of immune disorders [94, 95]. For example, Interferon β 1a, Rebif® is prescribed for multiple sclerosis  
[95]. Interferon (IFN) β-1a has been reported as highly effective in inhibiting in vitro SARS-CoV-2 replication at  
clinically achievable concentration when administered after virus infection. In vitro observations revealed that  
IFN-β-1a effectively inhibits both infectious virus particles and viral RNA on treated cells, when compared to  
virus-positive infection control without toxicity at its highest tested concentration [96]. The drug EC50  
evaluated at 48, 72, and 96 hours after infection is suggested to be easily accessed in the clinical setting to help  
address drug administration regimens in vivo [96].  
Authors' contributions  
E.GharibMombeni, S.Chekani-Azar and M.Yousefi conceived the main review on drugs and vaccines and  
MS.Abousenna edited vaccines section, and K.Armin, F.Shavandi, E.Emami and Y.Bahrami performed review on  
some of drugs and S.Chekani-Azar and E.GharibMombeni edited the final version of manuscript.  
Conflict of interest  
The authors declare that there is no conflict of interest.  
MacLachlan NJ, Dubovi EJ. In: NJ MacLachlan, EJ Dubovi, eds. Book title: Fenner's Veterinary Virology. 5th ed. Cambridge, MA:  
Academic Press; p. 393413. ISBN: 978-0-12-375158-4. 2017.  
Masters, Paul S. Book title: The molecular biology of coronaviruses. Advances in virus research, 66. 2006: p. 193-292. DOI:  
Siddell SG. Book title: The coronaviridae. Springer, 1995: p. 1-10. ISBN 978-1-4899-1531-3.  
4. De Groot RJ, Baker SC, Baric R, Enjuanes L, Gorbalenya A, Holmes KV, Perlman S, Poon L, Rottier PJ, Talbot PJ, Woo PC. Coronaviridae.  
Virus Taxonomy: ninth report of the International Committee on Taxonomy of Viruses. Secondary title: Elsevier Academic: London,  
United Kingdom; 2011:806-28. ISBN: 9780123846846.  
Burrell CJ, Howard CR and Murphy FA. Chapter 31 - coronaviruses. In: Burrell CJ, Howard CRandMurphy FA, editors. Book title:  
Fenner and White's Medical Virology . London: Academic Press, 2017: p. 437-446. ISBN: 9780123751560.  
6. World  
Corum J, Grady D, Wee S-LandZimmer C. Coronavirus vaccine tracker. The New York Times. 2020; 5.  
8. Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh C-L, et al. Cryo-em structure of the 2019-ncov spike in the prefusion conformation.  
Citation: Gharib Mombeni E, Yousefi M, Chekani-Azar S, Abousenna MS, Armin K, Shavandi F, Emami E and Bahrami Y. Recent drugs and vaccines candidates  
9. Mahase E. Covid-19: Moderna vaccine is nearly 95% effective, trial involving high risk and elderly people shows. BMJ: British Medical  
10. Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, et al. An mrna vaccine against sars-cov-2preliminary report. New  
11. Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, et al. Safety and efficacy of the bnt162b2 mrna covid-19 vaccine. New England  
12. Mahase E. Covid-19: Vaccine candidate may be more than 90% effective, interim results indicate. BMJ. 2020; 371: m4347. Link  
13. Anderson EJ, Rouphael NG, Widge AT, Jackson LA, Roberts PC, et al. Safety and immunogenicity of sars-cov-2 mrna-1273 vaccine in  
14. Mulligan MJ, Lyke KE, Kitchin N, Absalon J, Gurtman A, et al. Phase i/ii study of covid-19 rna vaccine bnt162b1 in adults. Nature. 2020;  
15. Cohen J. Vaccine designers take first shots at covid-19. Secondary title: American Association for the Advancement of Science; 2020.  
16. Zhang J, Zeng H, Gu J, Li H, Zheng L, et al. Progress and prospects on vaccine development against sars-cov-2. Vaccines. 2020; 8 (2):  
17. Baran I. Sars-cov-2 vaccine development strategies. Medical sciences and biotechnology book. 2020; 7: 65.  
18. Mertz L. One shot wonder:  
vaccine against all coronaviruses. IEEE pulse. 2020; 11 (6): 2-5. DOI:  
19. Bertin P, Nera KandDelouvée S. Conspiracy beliefs, rejection of vaccination, and support for hydroxychloroquine: A conceptual  
replication-extension in the covid-19 pandemic context. Frontiers in psychology. 2020; 11: 2471. DOI:  
20. Evenett SJ. Chinese whispers: Covid-19, global supply chains in essential goods, and public policy. Journal of International Business  
Policy. 2020; 3 (4): 408-429. DOI:  
21. Mucchielli L. Behind the french controversy over the medical treatment of covid-19: The role of the drug industry. Journal of Sociology.  
22. Shervani Z, Khan IandQazi UY. Sars-cov-2 delayed tokyo 2020 olympics: Very recent advances in covid-19 detection, treatment, and  
vaccine development useful conducting the games in 2021. Advances in Infectious Diseases. 2020; 10 (03): 56. DOI:  
23. Taxt AM, Grødeland G, Lind A, Müller F. Status of COVID-19 vaccine development. Tidsskrift for Den norske legeforening. 2020 Sep 23.  
24. Cohen J. New coronavirus threat galvanizes scientists. Secondary title: American Association for the Advancement of Science; 2020.  
25. Dwipayana IDAP. Efforts in securing vaccine for covid-19 outbreak in indonesia. Health Notions. 2020; 4 (10): 313-317. DOI:  
26. Xia S, Duan K, Zhang Y, Zhao D, Zhang H, et al. Effect of an inactivated vaccine against sars-cov-2 on safety and immunogenicity  
27. Zhang Y, Zeng G, Pan H, Li C, Hu Y, et al. Safety, tolerability, and immunogenicity of an inactivated sars-cov-2 vaccine in healthy adults  
aged 1859 years: A randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. The Lancet Infectious Diseases. 2020. DOI:  
28. van Doremalen N, Lambe T, Spencer A, Belij-Rammerstorfer S, Purushotham J, et al. ChAdOx1 nCoV-19 vaccination prevents SARS-  
29. Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, et al. Safety and efficacy of the chadox1 ncov-19 vaccine (azd1222) against  
sars-cov-2: An interim analysis of four randomised controlled trials in brazil, south africa, and the uk. The Lancet. 2020. DOI:  
30. Zumla A, Hui DS, Azhar EI, Memish ZAandMaeurer M. Reducing mortality from 2019-ncov: Host-directed therapies should be an  
31. Hui DSandZumla A. Severe acute respiratory syndrome: Historical, epidemiologic, and clinical features. Infectious Disease Clinics.  
32. Azhar EI, Hui DS, Memish ZA, Drosten CandZumla A. The middle east respiratory syndrome (mers). Infectious Disease Clinics. 2019; 33  
33. Huang C, Wang Y, Li X, Ren L, Zhao J, et al. Clinical features of patients infected with 2019 novel coronavirus in wuhan, china. The  
34. Li G, Fan Y, Lai Y, Han T, Li Z, et al. Coronavirus infections and immune responses. Journal of Medical Virology. 2020. DOI:  
35. Channappanavar RandPerlman S. Pathogenic human coronavirus infections: Causes and consequences of cytokine storm and  
Secondary title: Springer; 2017. p. 529-539. DOI  
36. Batawi S, Tarazan N, Al-Raddadi R, Al Qasim E, Sindi A, et al. Quality of life reported by survivors after hospitalization for middle east  
37. Ngai JC, Ko FW, Ng SS, TO KW, Tong M, et al. The longterm impact of severe acute respiratory syndrome on pulmonary function,  
38. Zumla A, Chan JF, Azhar EI, Hui DSandYuen K-Y. Coronavirusesdrug discovery and therapeutic options. Nature reviews Drug  
39. Beigel JH, Nam HH, Adams PL, Krafft A, Ince WL, et al. Advances in respiratory virus therapeuticsa meeting report from the 6th isirv  
Citation: Gharib Mombeni E, Yousefi M, Chekani-Azar S, Abousenna MS, Armin K, Shavandi F, Emami E and Bahrami Y. Recent drugs and vaccines candidates  
40. Zumla A, Azhar EI, Arabi Y, Alotaibi B, Rao M, et al. Host-directed therapies for improving poor treatment outcomes associated with  
the middle east respiratory syndrome coronavirus infections. Secondary title: Elsevier; 2015. DOI:  
41. Perrone F, Piccirillo MC, Ascierto PA, Salvarani C, Parrella R, et al. Tocilizumab for patients with covid-19 pneumonia. The single-arm  
42. Jones GandDing C. Tocilizumab: A review of its safety and efficacy in rheumatoid arthritis. Clinical medicine insights. Arthritis and  
43. de Cáceres C, Martínez R, Bachiller P, Marín LandGarcía JM. The effect of tocilizumab on cytokine release syndrome in covid-19  
44. Furuta Y, Komeno TandNakamura T. Favipiravir (t-705), a broad spectrum inhibitor of viral rna polymerase. Proceedings of the Japan  
45. Wang Y, Fan G, Salam A, Horby P, Hayden FG, et al. Comparative effectiveness of combined favipiravir and oseltamivir therapy versus  
oseltamivir monotherapy in critically ill patients with influenza virus infection. The Journal of infectious diseases. 2019. DOI:  
46. Minskaia E, Hertzig T, Gorbalenya AE, Campanacci V, Cambillau C, et al. Discovery of an rna virus 35exoribonuclease that is  
critically involved in coronavirus rna synthesis. Proceedings of the National Academy of Sciences. 2006; 103 (13): 5108-5113. DOI:  
47. Smith EC, Blanc H, Vignuzzi MandDenison MR. Coronaviruses lacking exoribonuclease activity are susceptible to lethal mutagenesis:  
48. Mastrangelo E, Pezzullo M, De Burghgraeve T, Kaptein S, Pastorino B, et al. Ivermectin is a potent inhibitor of flavivirus replication  
specifically targeting ns3 helicase activity: New prospects for an old drug. Journal of Antimicrobial Chemotherapy. 2012; 67 (8): 1884-  
50. Caly L, Druce JD, Catton MG, Jans DAandWagstaff KM. The fda-approved drug ivermectin inhibits the replication of sars-cov-2 in  
51. Warren TK, Jordan R, Lo MK, Ray AS, Mackman RL, et al. Therapeutic efficacy of the small molecule gs-5734 against ebola virus in  
52. Sheahan T, Sims A, Graham R, Menachery V, Gralinski L, et al. Broad-spectrum antiviral gs-5734 inhibits both epidemic and zoonotic  
53. Savarino A, Di Trani L, Donatelli I, Cauda RandCassone A. New insights into the antiviral effects of chloroquine. The Lancet infectious  
54. Yan Y, Zou Z, Sun Y, Li X, Xu K-F, et al. Anti-malaria drug chloroquine is highly effective in treating avian influenza a h5n1 virus  
55. Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, et al. Chloroquine is a potent inhibitor of sars coronavirus infection and  
56. Brown AJ, Won JJ, Graham RL, Dinnon KH, Sims AC, et al. Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic  
deltacoronaviruses with  
a highly divergent rna dependent rna polymerase. Antiviral Research. 2019; 169: 104541.  
57. Jordan PC, Stevens SKandDeval J. Nucleosides for the treatment of respiratory rna virus infections. Antiviral Chemistry and  
58. Sheahan TP, Sims AC, Leist SR, Schäfer A, Won J, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir,  
59. Wang M, Cao R, Zhang L, Yang X, Liu J, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus  
60. Mackenzie AH. Dose refinements in long-term therapy of rheumatoid arthritis with antimalarials. The American journal of medicine.  
1983; 75 (1): 40-45. DOI:  
61. Monteil V, Kwon H, Prado P, Hagelkrüys A, Wimmer RA, et al. Inhibition of sars-cov-2 infections in engineered human tissues using  
62. Dinnon KH, Leist SR, Schafer A, Edwards CE, Martinez DR, et al. A mouse-adapted sars-cov-2 model for the evaluation of covid-19  
63. Miao X, Luo Y, Huang X, Lee SM, Yuan Z, et al. A novel biparatopic hybrid antibody-ace2 fusion that blocks sars-cov-2 infection:  
64. Souza PF, Lopes FE, Amaral JL, Freitas CDandOliveira JT. A molecular docking study revealed that synthetic peptides induced  
conformational changes in the structure of sars-cov-2 spike glycoprotein, disrupting the interaction with human ace2 receptor.  
65. Kalhor H, Sadeghi S, Abolhasani H, Kalhor RandRahimi H. Repurposing of the approved small molecule drugs in order to inhibit sars-  
cov-2 s protein and human ace2 interaction through virtual screening approaches. Journal of Biomolecular Structure and Dynamics.  
66. Plante KS, Plante JA, Fernandez D, Mirchandani D, Bopp N, et al. Prophylactic and therapeutic inhibition of in vitro sars-cov-2  
67. Hutchison T, Yapindi L, Malu A, Newman RA, Sastry KJ, et al. The botanical glycoside oleandrin inhibits human t-cell leukemia virus  
type-1 infectivity and env-dependent virological synapse formation.  
Antivir Antiretrovir. 2019; 11 (3). DOI:  
68. Sheahan TP, Sims AC, Zhou S, Graham RL, Pruijssers AJ, et al. An orally bioavailable broad-spectrum antiviral inhibits sars-cov-2 in  
human airway epithelial cell cultures and multiple coronaviruses in mice. Science Translational Medicine. 2020; 12 (541). DOI:  
Citation: Gharib Mombeni E, Yousefi M, Chekani-Azar S, Abousenna MS, Armin K, Shavandi F, Emami E and Bahrami Y. Recent drugs and vaccines candidates  
69. Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw F-M, et al. The effectiveness of convalescent plasma and hyperimmune  
immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: A systematic review and exploratory meta-  
70. Van Griensven J, Edwards T, de Lamballerie X, Semple MG, Gallian P, et al. Evaluation of convalescent plasma for ebola virus disease in  
71. Mulangu S, Dodd LE, Davey Jr RT, Tshiani Mbaya O, Proschan M, et al. A randomized, controlled trial of ebola virus disease  
72. Baden LR and Rubin EJ. Covid-19the search for effective therapy. The New England Journal of Medicine; 2020. DOI:  
74. Chan JF-W, Yao Y, Yeung M-L, Deng W, Bao L, et al. Treatment with lopinavir/ritonavir or interferon-β1b improves outcome of mers-  
cov infection in a nonhuman primate model of common marmoset. The Journal of infectious diseases. 2015; 212 (12): 1904-1913. DOI:  
75. Chu C, Cheng V, Hung I, Wong M, Chan K, et al. Role of lopinavir/ritonavir in the treatment of sars: Initial virological and clinical  
76. Cao B, Wang Y, Wen D, Liu W, Wang J, et al. A trial of lopinavirritonavir in adults hospitalized with severe covid-19. New England  
77. Weston S, Coleman CM, Sisk JM, Haupt R, Logue J, et al. Broad anti-coronaviral activity of fda approved drugs against sars-cov-2 in  
78. Funnell SGP, Dowling WE, Muñoz-Fontela C, Gsell PS, Ingber DE, et al. Emerging preclinical evidence does not support broad use of  
79. Dagens A, Sigfrid L, Cai E, Lipworth S, Cheng V, et al. Scope, quality, and inclusivity of clinical guidelines produced early in the covid-19  
80. Zhao JP, Hu Y, Du RH, Chen ZS, Jin Y, Zhou M, Zhang J, Qu JM, Cao B. Expert consensus on the use of corticosteroid in patients with  
2019-nCoV pneumonia. Zhonghua jie he he hu xi za zhi=Chinese journal of tuberculosis and respiratory diseases. 2020; 43(3):183-4.  
81. Donnelly SC, Haslett C, Reid PT, Grant IS, Wallace WA, et al. Regulatory role for macrophage migration inhibitory factor in acute  
82. Fernandes A, Zin WandRocco P. Corticosteroids in acute respiratory distress syndrome. Brazilian journal of medical and biological  
83. Reddy K, O'Kane CandMcAuley D. Corticosteroids in acute respiratory distress syndrome: A step forward, but more evidence is  
84. Tang BM, Craig JC, Eslick GD, Seppelt IandMcLean AS. Use of corticosteroids in acute lung injury and acute respiratory distress  
systematic review and meta-analysis. Critical care medicine. 2009; 37 (5): 1594-1603. DOI:  
85. Arabi YM, Mandourah Y, Al-Hameed F, Sindi AA, Almekhlafi GA, et al. Corticosteroid therapy for critically ill patients with middle east  
respiratory syndrome. American journal of respiratory and critical care medicine. 2018; 197 (6): 757-767. DOI:  
86. De Benedictis FMandBush A. Corticosteroids in respiratory diseases in children. American journal of respiratory and critical care  
medicine. 2012; 185 (1): 12-23. DOI:  
87. Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, et al. Dexamethasone in hospitalized patients with covid-19-preliminary report.  
88. Goodman RB, Pugin J, Lee J, SandMatthay MA. Cytokine-mediated inflammation in acute lung injury. Cytokine & growth factor  
89. Rizvi S, Danic M, Silver MandLaBond V. Cytosorb filter: An adjunct for survival in the covid-19 patient in cytokine storm? A case  
90. Alharthy A, Faqihi F, Memish ZA, Balhamar A, Nasim N, et al. Continuous renal replacement therapy with the addition of cytosorb®  
cartridge in critically ill patients with covid19 plus acute kidney injury:  
A caseseries. Artificial Organs. 2020. DOI:  
91. Rieder M, Wengenmayer T, Staudacher D, Duerschmied DandSupady A. Cytokine adsorption in patients with severe covid-19  
92. Supady A, Duerschmied D, Bode C, Rieder M, Lother A. Extracorporeal cytokine adsorption as an alternative to pharmacological  
93. US Food and Drug Administration. CytoSorb® 300 mL Device Approved by FDA for Emergency Treatment of COVID-19. N (%) or  
94. Monk PD, Marsden RJ, Tear VJ, Brookes J, Batten TN, et al. Safety and efficacy of inhaled nebulised interferon beta-1a (sng001) for  
treatment of sars-cov-2 infection: A randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet Respiratory Medicine.  
95. Manfredonia F, Pasquali L, Dardano A, Iudice A, Murri L, et al. Review of the clinical evidence for interferon β 1a (rebif®) in the  
96. Clementi N, Ferrarese R, Criscuolo E, Diotti RA, Castelli M, et al. Interferon-β-1a inhibition of severe acute respiratory syndrome–  
coronavirus 2 in vitro when administered after virus infection. The Journal of infectious diseases. 2020; 222 (5): 722-725. DOI:  
Citation: Gharib Mombeni E, Yousefi M, Chekani-Azar S, Abousenna MS, Armin K, Shavandi F, Emami E and Bahrami Y. Recent drugs and vaccines candidates