SARS-CoV-2 drug resistance and therapeutic approaches

Abstract

In light of the transition of COVID-19 from a pandemic to an endemic phase, there is still a dire need to address challenges associated with drug resistance, particularly among immunocompromised and high-risk populations. This review explores the current state of research on SARS-CoV-2 drug resistance and underscores the ongoing need for effective therapeutic strategies. It critically evaluates existing knowledge on resistance mechanisms and therapeutic options, aiming to consolidate information and highlight areas for future research. By examining the complex interactions between the virus and its host, the review advocates for a multifaceted approach, including combination therapies, targeted drug development, and continuous surveillance of viral mutations. It also emphasizes the impact of evolving viral variants on antiviral efficacy and suggests adaptive treatment protocols. This review aims to enhance our understanding of SARS-CoV-2 drug resistance and contribute to more effective management of COVID-19 through a discussion of promising strategies such as drug repurposing and combination therapies.

Keywords: Antiviral drugs; Drug resistance; Resistance mechanism; SARS-CoV-2; Therapeutic strategies.

Fig. 1

Mutations that cause drug resistance in the SARS-CoV-2. Key mutations in the RNA-dependent RNA polymerase (nsp12) include E802D, which increases resistance to remdesivir by approximately 2.5-fold. Other mutations like S759A and V792I also contribute to remdesivir resistance. In the main protease (nsp5), mutations such as E166V and S144A significantly reduce the effectiveness of protease inhibitors like nirmatrelvir. These mutations disrupt critical interactions necessary for drug binding, leading to increased resistance.

Fig. 2

Therapeutic approaches to mitigate the SARS-CoV-2 drug resistance. These strategies include monoclonal antibodies, convalescent plasma, and interferons. Monoclonal antibodies, such as SA58 and TriSb92, show promise against Omicron variants when administered intranasally. Convalescent plasma therapy utilizes antibodies from recovered patients to treat or prevent severe COVID-19, particularly in immunocompromised individuals. Interferons, especially interferon-beta, are explored for their antiviral properties, with early administration recommended to prevent severe outcomes.