Nature: Mass screening found 21 existing anti-neo-coronavirus drugs!

As !---- of July 27, 2020, more than 16.25 million cases of newly confirmed pneumonia (COVID-19) have been confirmed worldwide, bringing the total number of deaths to more than 640,000It takes 12 to 18 months to develop a targeted vaccine, regardless of the new coronavirus SARS-CoV-2 mutation, while it is conservatively estimated that it may take more than 10 years to develop and approve new antiviral drugs from scratchTherefore, rescreening testing of drugs that have been clinically evaluated to treat COVID-19 is one of the most feasible and effective strategies availableOn July 24, 2020, a team of researchers from the Sanford Burnham Prebis Institute of Medicine and the University of Hong Kong in the United States published their latest findings in Nature on the treatment of COVID-19 drugs, identifying 100 small molecules that inhibit SARS-CoV-2 replication, including 21 known drugs that show a significant dose-response relationship, and 13 molecules that can be treated in patients with a achievable dose of inhibitory viral replicationAmong them, cysteine protease inhibitors MDL-28170, ONO 5334 and apilimod can be sactrophic in human iPSC-derived lung cell-like cells replication, apilimod in the primary human lung transplant model also showed antiviral efficacyTo develop the treatment for COVID-19, the researchers established a small molecular drug library containing 11987 small molecular drugs that are clinically in clinical or FDA-approved, by allowing these small molecular compounds to process Vero E6 cells infected with SARS-CoV-2 (the epithelial cells of the kidneys derived from African green monkeys) to assess their potential antiviral activity against SARS-CoV-2Eventually, the researchers screened 100 compounds to inhibit at least 40 percent of viral replication, including viformacid receptor agonists (LGD-1550, Via acid, thabaratin, AviA, thajaratin, RBAD), Aldoglycese reductase inhibitors AL3152, benzodiazepine seisan agonists (ZK-93426, Zalaplon GR, Pagoron) and antimalarial drugs (AQ-13, hanfangchin A), etcHigh-throughput screening of SARS-CoV-2 antiviral drugs takes into account the expected therapeutic dose of these drugs, and the researchers conducted dose reaction analysis to determine the relationship between compound concentration and antiviral activityTwenty-one compounds, including Redsewe, were found to have significant dose-dependent antiviral activityTesting whether these drugs in-existing dose responses have potential synergies with Redsivir's antiviral action, screening four compounds has significant synergies with Redsivir, which is currently regulated for COVID-19 treatmentAfter the dose-reaction relationship of the selected antiviral drug and its synergy with Redsewe, the researchers further assessed the effectiveness of the 21 compounds on two other human cell lines that can be infected with SARS-CoV-2, and found that 19 of them inhibited viral replication in one or both cell lines, with efficacy equal to or greater The effectiveness of Vero E6 cells, 13 compounds can be in at least one cell line in the body can be achieved dose-suppressing virus replication, of which the five most effective inhibitory viruses are apilimod, VBY-825, ONO 5334, Z LVG CHN2 and MDL 28170It is necessary to evaluate the efficacy of the drug in different and appropriate models, so the researchers further assessed their antiviral activity in the human iPSC-derived lung cell-like cells, and found that the virus replication of these primary cell types decreased significantly after antiviral drug treatment, the number of infected cells treated by ONO 5334 decreased by 72%, and MDL 28170 was reducedThe antiviral activity of the most effective apilimod was re-evaluated in the outliopulmonal culture system and found that it was effective against the SARS-CoV-2 replication of the virus replication in the main tissue"This study greatly expands the treatment options of patients with COVID-19, as many of the small molecules screened already have human clinical safety data that may help control the global pandemic of COVID-19," said Sumit KChanda, a communications author of the report on evaluating antiviral activity in human cell models