A virtual screening approach using docking and free energy pertubation was successfully validated with previously characterized inhibitors of SARS-CoV-2 main protease (Mpro). This approach and then used to estimate the binding affinity to Mpro of more than 6300 compounds in the ZINC15 database. Delamanid, an anti-tuberculosis agent, has a predicted nanomolar binding affinity for SARS-CoV-2 Mpro and is thus a promissing drug candiate for COVID-19. In addition, several compounds including three antibiotics exhibits femtomolar affinity for SARS-CoV-2 Mpro. The residues around positions 24, 45, 143, 165, and 190 were found to be involved in the binding of the strongest inhibitors.

SARS-CoV-2 rapidly infects millions of people worldwide since December 2019. There is still no effective treatment for the virus, resulting in the death of more than one million of patients. Inhibiting the activity of SARS-CoV-2 main protease (Mpro), 3C-like protease (3CLP), is able to block the viral replication and proliferation. Although the dimer was shown to be the biologically active form of the SARS-CoV-2 Mpro, in this context, our study has revealed that <i>in silico</i> screening for inhibitors of SARS-CoV-2 Mpro can be reliably done using the monomeric structure of the receptor. Docking and fast pulling of ligand (FPL) simulations for both monomeric and dimeric forms correlate well with the corresponding experimental binding affinity data of 30 compounds. In particular, the correlation coefficients between computational and experimental binding free energy of the monomeric SARS-CoV-2 Mpro are approximately similar to the dimeric target. Moreover, the correlation coefficient between the rupture forces to binding free energy are roughly the same. Furthermore, the correlation coefficient between calculated metrics of the monomeric and dimeric SARS-CoV-2 Mpro is R = 0.74. Our study results show that it is possible to speed up computer-aided drug design for SARS-CoV-2 Mpro by focusing on the monomeric form instead of the larger dimeric one.

The vertical tyre force is crucial to the study of the dynamics of a tractor semi-trailer. The paper presents an experimental method for determining the vertical tyre force by determining the vertical acceleration of the un-sprung mass and the vertical acceleration of the sprung mass when the tractor semi-trailer moves. The results of this study form the basis for determining the dynamic tyre force without the installing of sensors on road.

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