The global impact of the COVID-19 pandemic caused by SARS-CoV-2 necessitates innovative
strategies for the rapid development of effective treatments. Computational methodologies, such as molecular
modelling, molecular dynamics simulations, and artificial intelligence, have emerged as indispensable tools in
the drug discovery process. This review aimed to provide a comprehensive overview of these computational
approaches and their application in the design of antiviral agents for COVID-19. Starting with an examination
of ligand-based and structure-based drug discovery, the review has delved into the intricate ways through
which molecular modelling can accelerate the identification of potential therapies. Additionally, the investigation
extends to phytochemicals sourced from nature, which have shown promise as potential antiviral agents.
Noteworthy compounds, including gallic acid, naringin, hesperidin, Tinospora cordifolia, curcumin, nimbin,
azadironic acid, nimbionone, nimbionol, and nimocinol, have exhibited high affinity for COVID-19 Mpro and
favourable binding energy profiles compared to current drugs. Although these compounds hold potential, their
further validation through in vitro and in vivo experimentation is imperative. Throughout this exploration, the
review has emphasized the pivotal role of computational biologists, bioinformaticians, and biotechnologists in
driving rapid advancements in clinical research and therapeutic development. By combining state-of-the-art
computational techniques with insights from structural and molecular biology, the search for potent antiviral
agents has been accelerated. The collaboration between these disciplines holds immense promise in addressing
the transmissibility and virulence of SARS-CoV-2.