A review on the mechanism of action of favipiravir and hydroxychloroquine in COVID-19

Abstract

The global COVID-19 pandemic, caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), spread rapidly across the globe. The lack of available therapies was an essential condition to repurpose available medicines for the treatment or prevention of that worrisome condition. It was our aim to summarize the available knowledge about the mechanism of action of the antirheumatic drugs chloroquine/hydroxychloroquine and the antiviral drug favipiravir. Further, the concomitant therapeutic potential of both drugs is discussed. The multiple mechanisms of action of CQ/HCQ as well as their immunomodulatory properties are still under investigation in COVID-19 treatment. The nucleoside analogue favipiravir is rapidly metabolized in host cells which disrupts viral synthesis and leads to mutagenesis. Clinical trials become available that provide evidence of the beneficial effect of concomitant use of both drugs in mild-COVID-19 patients. Simultaniously, side effects like QTc prolongation or teratogenicity pose risk to extensive community application. Future well designed, large randomized clinical trials are awaited to determine the role if any of those medications in COVID-19 therapy.

A Clinical Insight on New Discovered Molecules and Repurposed Drugs for the Treatment of COVID-19

“…Hydroxychloroquine blocks sialic acid receptors at the upper respiratory pathway and prevents the glycosylation of the angiotensin converting enzyme 2 (ACE2) receptor [ 116 , 117 , 118 , 119 ]. Prevention of ACE2 receptor glycosylation results in the failure of the viral spike protein binding to the ACE2 receptor.…”

“…Favipiravir is a prodrug that is biotransformed into its active metabolite favipiravir ribofuranosyl-5′-triphosphate (favipiravir-RTP). Favipiravir-RTP interacts with RdRp and blocks the replication cycle of the virus genome [ 78 , 118 , 131 ]. Till now, the interaction mechanism is not very clear, but a hypothesis regarding it claims that this active metabolite may link to the conserved domains of polymerase, or it may be added in a nascent viral RNA, for which nucleotides cannot be added, and the process of transcription and replication is blocked.…”

“…Remdesivir (7.6% patients) showed more beneficial effects than dexamethasone (22.9% patients) in reducing the death rate, but adverse events for dexamethasone (12.7% of patients) were lesser than remdesivir (24.6% of patients). Like remdesivir, favipiravir also blocks RdRp to combat COVID-19 [ 78 , 118 , 131 ]. Due to its good efficacy in inhibiting viral proliferation, favipiravir protects the lungs from fibrosis and inflammatory damage [ 157 ].…”

A Green Eco-friendly Analytical Method Development, Validation, and Stress Degradation Studies of Favipiravir in Bulk and Different Tablet Dosages Form by UV-spectrophotometric and RP-HPLC Methods with their Comparison by Using ANOVA and in-vitro Dissolution Studies

“…5 The mechanism action of favipiravir has been observed in two ways by induction of lethal mutagenesis and by RNA chain termination and incorporation of T-705 in the viral RNA strand. 6 Favipiravir (prodrug) is a purine base analog that undergoes intracellular phosphoribosylation to become active favipiravir ribofuranosyl-5B-triphosphate (favipiravir-RTP), which can prevent SARS-CoV, MERS-CoV, and other RNA virus infections by directly inhibiting viral transcription and replication. 7 In pharmacokinetics studies, favipiravir shows significant bioavailability (>94%), a modest volume of distribution, and a 54% protein binding rate (10e20 L).…”