Computational Purposing Phytochemicals against Cysteine Protease of Monkeypox Virus: An In-silico Approach

Abstract

The development and evolution of viruses that cause disease have presented a formidable challenge to contemporary medicine and the global economy, not to mention a catastrophic risk to human health. Almost all of these viruses are zoonotic, meaning they were first identified in animals and then spread to humans. An emerging virus may cause only a few isolated instances, resulting in a limited outbreak, or it may cause widespread infection and spread to other parts of the world, triggering a full-blown epidemic. These kinds of emerging occurrences have occurred frequently and in many different forms during the past few decades. Monkeypox is a zoonotic disease caused by the monkeypox virus, a member of the orthopox family that also includes variola, cowpox, and vaccinia. Both animals and humans can get infected by this virus. Similar to smallpox this disease shows less severe rashes and lower mortality rate. The outbreak of monkeypox was declared a global public health emergency by the World Health Organization in July 2022. Unknown mutations and variations are linked to the recent epidemic. Presently, FDA approved tecovirimat, cidofovir and brincidofovir are there in market to treat monkeypox virus. But there are some side effects of these drugs as they are synthetic. So, scientists are working on natural remedies that can be used as alternative to these drugs. In the present study virtual screening of phytochemicals (N-(2-Allylcarbamoyl-4-chloro-phenyl)-3,4-dimethoxy-benzamide, 6-Dimethylaminonaphthene-1-sulfonicacid amide, Oleic Acid and dipentyl ester) from Allophylus serratus were employed against core viral cysteine proteases from monkeypox virus was done. The docking study revealed that selected ligands bind with target viral protein with binding affinity in the range of -5.0 to -6.7 kcal/mol. N-(2-Allylcarbamoyl-4-chloro-phenyl)-3,4-dimethoxy-benzamide showed the highest binding affinity of -6.7 kcal/mol which can be investigated in the future to design potential drugs against monkeypox virus. Thus, this study foresees the possibility of bioactive phytochemicals functioning as template molecules for further experimental evaluation of their efficiency against monkeypox virus.

Structural and functional insights into the helicase protein E5 of Mpox virus

“…Many small molecule inhibitors have been designed to target the proteins important for the life cycle of MPXV, such as the DNA ploymerase, Topisomerase 1, and Cysteine proteinases 49 , 50 . However, these molecules mainly target the catalytic site of the protein, which is largely conserved in the homologous proteins in the host.…”

Molecular docking of monkeypox (mpox) virus proteinase with FDA approved lead molecules

“…In addition, using molecular docking and molecular dynamics simulations, four potential inhibitors—Tipranavir, Cefiderocol, Doxorubicin, and Dolutegravir—were identified as candidates for repurposing against the mpox virus. In a study, Bansal et al [25] tested phytochemicals from Allophylus serratus against core viral cysteine proteases from mpox virus. These compounds included N-(2-Allylcarbamoyl-4-chloro-phenyl)-3,4-dimethoxy-benzamide, 6-Dimethylaminona phthene -1-sulfonicacid amide, and Oleic Acid.…”

Repurposing Anti-Dengue Compounds against Monkeypox Virus Targeting Core Cysteine Protease

“…A modelled protein structure of cysteine protease was used in structure-based drug design to screen phytochemicals against the MPXV [53]. This study discussed the application of molecular docking that identified N-(2-Allylcarbamoyl-4-chloro-phenyl)-3,4-dimethoxybenzamide, which exhibited promising molecular binding results.…”