Computational prediction of phytochemical inhibitors against the cap-binding domain of Rift Valley fever virus.

Rift Valley fever is a zoonotic disease that can spread through livestock and mosquitoes, and its symptoms include retinitis, photophobia, hemorrhagic fever and neurological effects. The World Health Organization has identified Rift Valley fever as one of the viral infections that has potential to cause a future epidemic. Hence, efforts are urgently needed toward development of therapeutics and vaccine against this infectious disease. Notably, the causative virus namely, the Rift Valley fever virus (RVFV), utilizes the cap-snatching mechanism for viral transcription, rendering its cap-binding domain (CBD) as an effective antiviral target. To date, there are no published studies towards identification of potential small molecule inhibitors for the CBD of RVFV. Here, we employ a virtual screening workflow comprising of molecular docking and molecular dynamics (MD) simulation, to identify 5 potential phytochemical inhibitors of the CBD of RVFV. These 5 phytochemical inhibitors can be sourced from Indian medicinal plants, Ferula assa-foetida, Glycyrrhiza glabra and Leucas cephalotes, used in traditional medicine. In sum, the 5 phytochemical inhibitors of the CBD of RVFV identified by this purely computational study are promising drug lead molecules which can be considered for detailed experimental validation against RVFV infection.

In silico identification of potential inhibitors of vital monkeypox virus proteins from FDA approved drugs.

The World Health Organization (WHO) recently declared the monkeypox outbreak 'A public health emergency of international concern'. The monkeypox virus belongs to the same Orthopoxvirus genus as smallpox. Although smallpox drugs are recommended for use against monkeypox, monkeypox-specific drugs are not yet available. Drug repurposing is a viable and efficient approach in the face of such an outbreak. Therefore, we present a computational drug repurposing study to identify the existing approved drugs which can be potential inhibitors of vital monkeypox virus proteins, thymidylate kinase and D9 decapping enzyme. The target protein structures of the monkeypox virus were modelled using the corresponding protein structures in the vaccinia virus. We identified four potential inhibitors namely, Tipranavir, Cefiderocol, Doxorubicin, and Dolutegravir as candidates for repurposing against monkeypox virus from a library of US FDA approved antiviral and antibiotic drugs using molecular docking and molecular dynamics simulations. The main goal of this in silico study is to identify potential inhibitors against monkeypox virus proteins that can be further experimentally validated for the discovery of novel therapeutic agents against monkeypox disease.