Exploring the chemical space for potential inhibitors against cell surface binding protein of Mpox virus using molecular fingerprint based screening approach

Mpox virus is the latest member of the Poxviridae family of which small pox virus is a member. Monekypox virus has led to thousands of infections across the globe. Poxvirus gains entry into the cell making use of glycosaminoglycans like chondroitin sulphate and heparan sulphate. The interaction of the Mpox virus protein E8L also called cell surface binding protein is crucial for host cell attachment, membrane fusion and viral entry into the host cell leading to establishment of infection thus making this protein a very attractive therapeutic target. In this study we have tried to utilize the chondroitin sulphate binding groove present in the protein and identify molecules which are structurally similar to chondroitin sulphate. These molecules can thus occupy the same pocket but with a better binding affinity than chondroitin sulphate in order to outcompete the latter molecule from binding to the E8L protein and thus prevent it from performing its function. This study may pave the way for development of highly efficient therapeutics against the Mpox virus and further curb its infective potential.Communicated by Ramaswamy H. Sarma

Automated summary

The Mpox virus is a member of the Poxviridae family and has caused thousands of infections globally. It enters cells by utilizing glycosaminoglycans, such as chondroitin sulfate and heparan sulfate. The interaction of the cell surface binding protein E8L of the Mpox virus is crucial for host cell attachment, membrane fusion, and viral entry, making it a promising target for therapeutic intervention. This study aims to identify molecules structurally similar to chondroitin sulfate that can outcompete its binding to the E8L protein and potentially serve as highly efficient therapeutics against the Mpox virus, reducing its infective potential.