A computational study of metal–organic frameworks (MOFs) as potential nanostructures to combat SARS-CoV-2

The COVID-19 causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a critical surface protein called spike protein (S protein), which is the target of many vaccines and drugs developments. Among non-structural proteins of SARS-CoV-2, main protease (M(pro)) has drawn much attention to itself for designing antiviral drugs since it is very crucial for the virus replication in host cells. In the first part of the present study, the application of metal–organic frameworks (MOFs), one of the developing nanomaterials in the deformation and consequently inhibition of S protein binding to the receptor, angiotensin-converting enzyme 2 (ACE 2), is investigated. In this line, various S protein inhibitors were designed virtually, including ZIF, UIO, and IRMOF that their interactions with S protein and were investigated using molecular dynamics (MD) simulation. The results revealed that ZIF is the best candidate among the investigated MOFs with the least amount of energy interference with S protein. In the second part, the interaction of three-dimensional (3D) MOFs (such as ZIF, IRMOF, and HKUST) with SARS-CoV-2 M(pro) was investigated. HKUST had the most potent interaction with M(pro) and showed more promise in deforming this protein's secondary structure among all materials tested. Furthermore, we investigated the interaction of HKUST-OH with M(pro) to determine the effect of functionalization. The findings of this study could be used in future studies to introduce bioconjugates of MOFs and biological molecules (e.g., antibody or nanobody) or to use MOFs as carriers for antiviral drug delivery.