A novel virtual screening procedure identifies Pralatrexate as inhibitor of SARS-CoV-2 RdRp and it reduces viral replication in vitro

Abstract

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus poses serious threats to the global public health and leads to worldwide crisis. No effective drug or vaccine is readily available. The viral RNA-dependent RNA polymerase (RdRp) is a promising therapeutic target. A hybrid drug screening procedure was proposed and applied to identify potential drug candidates targeting RdRp from 1906 approved drugs. Among the four selected market available drug candidates, Pralatrexate and Azithromycin were confirmed to effectively inhibit SARS-CoV-2 replication in vitro with EC50 values of 0.008μM and 9.453 μM, respectively. For the first time, our study discovered that Pralatrexate is able to potently inhibit SARS-CoV-2 replication with a stronger inhibitory activity than Remdesivir within the same experimental conditions. The paper demonstrates the feasibility of fast and accurate anti-viral drug screening for inhibitors of SARS-CoV-2 and provides potential therapeutic agents against COVID-19.

Potent inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 by photosensitizers compounds

“…The procedure was similar to our previously published report[ 21 ]. Briefly, vero cells were fixed in 4% formaldehyde at 48th h.p.i.…”

“…Firstly, the titer of the viral stock was measured by 50% tissue culture infective dose (TCID 50 ), then the antiviral activities of the photosensitizers were evaluated as previously reported with some modifications[ 21 ]. Vero cells were seeded in a 24-well transparent plate 24 hr before infection.…”

Overview of current state of research on the application of artificial intelligence techniques for COVID-19

“… Zhang et al (2020) used fully connected ANN to envisage binding affinities from the PDBbind database. They explored the existing molecules for the treatment of SARS-CoV-2 ( Zhang et al, 2020 ). Beck et al (2020) developed Molecule Transformer-Drug Target Interaction (MT-DTI) model to determine antivirals drugs that may be effective against coronavirus.…”

Potent Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by photosensitizers

“…Evaluation of antiviral activities of the photosensitizers using the live virus Firstly, the titer of the viral stock was measured by 50% tissue culture infective dose (TCID 50 ), then the antiviral activities of the photosensitizers were evaluated as previously reported with some modi cations 19 . Vero cells were seeded in a 24-well transparent plate 24 hr before infection.…”

“…Immuno uorescence assay 19 Vero cells were xed in 4% formaldehyde at 48th h.p.i. Then cells were permeabilized in 0.5% Triton X-100, blocked in 5% BSA in PBS, and then probed with the plasma of this patient or healthy control at a dilution of 1:500 for 1 h at room temperature.…”