Atazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine production

Natalia Fintelman-Rodrigues; Carolina Q. Sacramento; Carlyle Ribeiro Lima; Franklin Souza da Silva; André C. Ferreira; Mayara Mattos; Caroline S. de Freitas; Vinicius Cardoso Soares; Suelen da Silva Gomes Dias; Jairo R. Temerozo; Milene Miranda; Aline R. Matos; Fernando A. Bozza; Nicolas Carels; Carlos Roberto Alves; Marilda M. Siqueira; Patrícia T. Bozza; Thiago Moreno L. Souza

. CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.04.020925 doi: bioRxiv preprint 1 4 Since the tertiary structure (3D) of the SARS-CoV-2 Mpro is a homodimer, we focused the molecular dynamics only one chain, henceforward chain A. Molecular dynamics calculations were performed using NAMD 2.9 49 and Charmm27* force field 50 at pH 7, i.e., with deprotonated Glu and Asp, protonated Arg and Lys, and neutral His with a protonated Nε atom. This all-atom force field has been able to fold properly many soluble proteins [51] [52] [53] . The soluble proteins were centered in a cubic box of TIP3P water molecules 54 ; the box extended 1.2 nm outside the protein on its four lateral sides, and the appropriate numbers of Na+ and Cl-ions were added to ensure system neutralization. The electrostatic interactions were calculated using the Particle Mesh Ewald method and a cutoff of 1.2 nm 55 . The same cutoff of 1.2 nm was used for the Van der Waals interactions. The non-bonded pair lists were updated every 10 fs. In what follows, the analysis is based on MD simulation of 100 ns at 310 K.