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

Abstract

Potential clinical benefit in SARS-CoV-2 infection upon remdesivir treatment has been established. Recently, FDA has granted full approval for the clinical use of remdesivir for COVID therapy. However, the efficacy of remdesivir alone or in combination with other antivirals is still open to research, especially in terms of benefits vs. risk ratio. We here review remdesivir therapy based on 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 treatments have also been taken into consideration. We found promising in vitro evidence for efficacy of remdesivir, in combination with (hydroxy) chloroquine and/or favipiravir against SARS-CoV-2 infection in cell culture studies. However, clinical trial results from these combinations were not in line with the promising in vitro data, and therefore limit the use of such combinations in practice. Remdesivir and antibody therapies have also been used clinically either in combination or in sequential application. However, there are no substantive evaluable clinical data on these uses as of now. Additionally, some other drug combinations with remdesivir have been proposed in this article for future improvement in therapies.

A New Antiviral Regimen Against SARS-CoV-2 Based on Nanoviricide’s Biopolymer (NV-CoV-2)

“…The antiviral efficacy and potency and the cytotoxicity of the antiviral compound NV-CoV-2 in cell cultures were studied (Li et al, 2007;Barton et al, 2011Barton et al, , 2016Chakraborty and Diwan 2020a;Chakraborty and Diwan 2020b;Diwan et al, 2021b). Relative CPE levels were compared between all groups to identify any reduction in viral replication, as a reduction in CPE compared to untreated infected controls suggests a decrease in virus production/growth/spread.…”

“…Proof-of-concept studies were conducted in CoV-NL63-infected cell in cultures and also in virus-infected rats (Chakraborty and Diwan 2020a;2020b) as the SARS-CoV-2 and CoV-NL63 bind to the same receptor, angiotensin-converting enzyme 2 (ACE2), for entry into the host cells (Li et al, 2007). With several studies, both in vitro and in vivo, we have shown that encapsulation of RDV in NV-CoV-2 and the stability of RDV as well as its overall antiviral efficacy of the proposed regimen has improved a lot (Chakraborty and Diwan 2020a;2020b).…”