Impacts of the Omicron Variant on the Effectiveness of Direct-Acting Antivirals: Replication-Inhibiting Small Molecules and Antibody-Based Therapeutics

Abstract

Since the beginning of the COVID-19 pandemic, researchers have made great progress with the development of direct-acting antiviral therapies, which are divided into two categories: small molecules targeting the SARS-CoV-2 replication machinery and monoclonal antibodies targeting the spike protein. Through rigorous clinical trials, a small number of antivirals in development have been approved in different countries. The first category of approved therapeutics is direct-acting small molecules, including the replication inhibitors Remdesivir and Molnupiravir and the 3CLpro inhibitor Paxlovid. The second category is monoclonal including Bamlanivimab, Casirivimab and imdevimab, and Sotrovimab. The effectiveness of these therapeutics is being challenged by the emergence of the Omicron Variant. Since the Omicron Variant emerged recently in November 2021, the impacts of the new mutations on the activity of antiviral therapeutics are largely unknown. It is important to investigate antivirals because they are key to reducing the severity of disease and preventing hospitalization and deaths. This article will investigate the following questions. 1) How is the effectiveness of replication-targeting small molecules being impacted by the Omicron variant? 2) How is the effectiveness of antibody-based therapy being impacted by the Omicron variant? By answering these questions, the current state of commonly used antivirals in the face of the Omicron-dominated wave of infections could be better understood, helping to determine the best way to allocate and distribute antivirals efficiently. The Omicron variant is changing the playing field for antiviral drugs. Because of this, hospitals need to adapt their arsenal of antiviral drugs.