Role of structure-based drug design (SBDD) in the repurposing and discovery of anti-viral leads against Monkeypox virus disease

The rising prevalence of positive Monkeypox (MPOX) infection cases worldwide is a considerable cause for alarm. MPOX is due to the monkeypox virus (MPXV), a zoonotic pathogen within the Orthopoxvirus genus, primarily found in central and western Africa. Recently, it has disseminated globally, which has aroused the interest of the scientists due to its transfer to people and its severe clinical manifestations. The accessibility of the entire genome sequence of MPXV facilitated the identification of valuable targetable proteins within the MPXV lifecycle that substantially aid in the repurposing, design, and development of therapies to manage this issue. Computer-Aided Drug Design (CADD), particularly Structure-Based Drug Design (SBDD), now serves as a fundamental component of pharmaceutical discovery pipelines. Nowadays, the SBDD approach facilitates the systematic analysis of biochemical and interaction processes relevant to pharmaceuticals at the molecular scale. Although there are no specific approved MPOX drugs, here we present a thorough summary of current research on small molecules, encompassing both conventional and novel platforms. The significance and approach of SBDD are emphasized by highlighting protein-ligand interactions, molecular docking, dynamic simulations, and ADMET prediction in the identification of prospective therapeutic candidates. An exhaustive and updated database of repurposed and newly proposed lead compounds toward MPXV is generated. Providing researchers with this comprehensive knowledge highlights the significance of creative techniques and interdisciplinary collaborations in tackling the problems posed by MPXV as research progresses. However, it could be emphasized that very few in silico outcomes were corroborated by in vitro studies to confirm the efficiency of the selected compounds. This needs more collaborative effort between computational and experimental researchers and institutions to facilitate the closure of this gap. Graphical abstract