Pharmacodynamics of Remdesivir: How to Improve for COVID-19 Treatment

A Chakraborty,A Diwan

doi:10.37871/jbres1175

Abstract

Potential clinical benefit in SARS-CoV-2 with remdesivir have been noticed. Recently, FDA has granted the use of remdesivir for COVID-therapy. However, the efficacy of remdesivir alone or with combination of other antivirals, like chloroquine or hydroxychloroquine is still questionable, especially in terms of benefits vs. risk ratio. We here did a search for relevant pharmacological evidences with regards to the Pharmacokinetics (PK) and Pharmacodynamics (PD) of appropriate antiviral compounds against COVID-19 alone or in combination with other potential therapies. Drug–Drug Interactions (DDIs), if any in case of combo treatment have also been taken into consideration. We found promising in vitro evidence for using remdesivir, in combination with (hydroxy) chloroquine and/or favipiravir against SARS-CoV-2. However, clinical trial results are not that satisfactory as expected and limit the use in practice. Additionally, some other drug combination with remdesivir have been proposed in this article for future improvement in therapies.

Highlights

Drugs active against SARS-CoV-2The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that causes COVID-19 was declared as a global pandemic on 11 March 2020, by the WHO, the evidence for therapies against this virus is as yet inadequate
The combo drug effect of remdesivir and ribavirin were tested on Middle East Respiratoy Syndrome (MERS)-CoV and SARS-CoV
One of the coronavirus strains (h-CoV-NL63) that we studied, uses the same cell surface receptor ACE2 that is shared by SARS-CoV-2 and SARS-CoV-1

Summary

Introduction

Drugs active against SARS-CoV-2The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that causes COVID-19 was declared as a global pandemic on 11 March 2020, by the WHO, the evidence for therapies against this virus is as yet inadequate. How to cite this article: Chakraborty A, Diwan A. Therapeutic agents available for COVID-19 can have other treatment challenges, drugdrug interactions. Several compounds that have been proposed for the treatment of SARS-CoV-2 are affected by the Cytochrome P450 (CYP)-metabolizing system as an either substrate, enzyme inhibitor or enzyme inducer [2]. The dosing requirements of concomitant SARS-CoV-2 or other supportive drug therapies should be evaluated properly based on the above–mentioned possible drug-drug interaction, at least for non-novel compounds. Lopinavir/Ritonavir (LPV/r), a strong inhibitor of CYP3A4 and CYP2D6, can metabolize hydroxychloroquine (an antiviral against SARS-CoV-2) and exhibited a potential toxicity in an animal model [2]

Results

Discussion

Conclusion