3- Inhibition of viral replication
Hydroxychloroquine inhibits virus replication in different steps: inhibition of the fusion of the virus to its receptor, inhibition of the nucleic acid replication, virus assembly, and virus release (32). In a study, the therapeutic plan was using hydroxychloroquine for 5 days; the results supported the application for SARS-CoV-2 infection treatment (31). Another study which used hydroxychloroquine for 3 to 6 days, showed that it could decrease viral load reduction in COVID-19 patients. Also, a combination of hydroxychloroquine and azithromycin had synergic effects on viral elimination (32, 33). Other antiviral treatments are as follows:
a) Ribavirin and interferon‐β , are virus replication inhibitors in animals and human cell lines. Adverse effects of ribavirin include hemolytic anemia and decreased hemoglobin. It is contraindicated in pregnant patients.
b) Lopinavir/ritonavir (Kaletra) : Lopinavir/ritonavir (LPV/RTV) is a combination of lopinavir and ritonavir (34). RTV inhibits the CYP3A‐mediated metabolism of LPV, thereby increasing the serum concentration of LPV(35). This combination reduces coronavirus viral loads remarkably(36). LPV inhibits polyprotein processing in CoV(34). SARS‐CoV2 and SARS‐CoV share a 79.5% sequence identity. LPV is useful for treating SARS and MERS patients, so it may be useful in COVID-19 patients, too. Chu et al have found out that the use of LPV/ RTV with ribavirin showed better results in the treatment of SARS (34). Deng et al found that 16 patients who received arbidol and LPV/RTV had better clinical manifestation than LPV/RTV only (35). Caution should be taken when taking Kaletra, since it can result in upper respiratory tract infection, vasodilation, thrombocytopenia, neutropenia, stevens-Johnson syndrome, transaminase increase, and a possible increase in myocardial infarction (28, 37).
c) Remdesivir : Remdesivir is an adenosine triphosphate analogue and a broad-spectrum antiviral which affects viral RNA polymerase and terminates RNA transcription. (38-40). It was primarily developed for Ebola treatment and demonstrated effectiveness against SARS and MERS in animal models. A combination of remdesivir (RDV) and interferon‐β have shown stronger antiviral activity against MERS‐CoV to that of Lopinavir/ritonavir and IFN‐β. Also, remdesivir unlike LPV/RTV‐IFN‐β, could reduce lung viral loads against MERS in animal study (8, 41). It is currently under several clinical trials for assessing its efficacy against COVID-19. Toxicity and adverse effects are under investigation.
d) Oseltamivir : The strategy that has been tried so far showed that 75 patients were administrated 75 mg oseltamivir, 500 mg ritonavir, 500 mg lopinavir, and the intravenous administration of 0.25 g ganciclovir for 3–14 days twice a day (11). In a case series in Wuhan, China, most of the patients have been treated by oseltamivir, moxifloxacin, ceftriaxone, and azithromycin. Some of them received glucocorticoid therapy. Discharge rate of 34.1% and the mortality rate of 4.3% have been observed (17). The benefits of Oseltamivir on the course of treatment was unknown (42).
e) Favipiravir is a broad-spectrum antiviral drug that inhibits viral replication. Favipiravir treatment increased the survival rate and decreased viral load. Favipiravir has potential drug-drug interactions and in patients with basic diseases have to pay attention(43). Favipiravir is contraindicated in pregnancy(44).