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April 13, 2020 / / - Severe Acute Respiratory Syndrome (SARS-CoV-2) is the pathogen that causes the current epidemic of COVID-19, which causes 10 times as many deaths as other public health emergencies of international concern caused by highly pathogenic CoV in 2002 and 2012.
addition to social isolation, the re-use of appropriate clinically approved drugs can lead to short-term action to reduce mortality.
sars-CoV-2 main protease (Mpro) is the target of highly pathogenic CoV.
HIV protease inhibitors, such as LPV, can also inhibit THES-CoV Mpro in 2002.
, however, it is not clear whether other clinically approved antiretroviral protease inhibitors can bind more effectively to this enzyme to prevent sars-CoV-2 replication, and there is no evidence.
photo source: BioRxiv Among these substances, the bio-utilization of Atazanavir (ATV) into the respiratory tract has been documented, which has inspired researchers from Brazil to further assess its ability to replicate SARS-CoV-2.
recently, the researchers published their findings on the preprinted platform bioRxiv, entitled "Atazanavir reseds SARS-CoV-2 replication and pro-lyaty cytokine production".
In this study, researchers used molecular dynamic analysis to find that ATV is more capable of binding to SARS-CoV-2 Mpro active bits than Lopinave, and that ATV has always occupied the substrate gap of SARS-CoV-2 Mpro active bits throughout molecular dynamics analysis.
in a cell-free protease experiment, the researchers found that ATV inhibited Mpro activity at a concentration of 10 μM.
researchers have found in cell experiments that ATV inhibits the replication of SARS-CoV-2 in different types of cells -- Vero cells, human pulmonary endotythells, and human progenitor monocytes -- whether combined with litonave or not.
In addition, the researchers found that these drugs were effective in suppressing elevated levels of virus-induced IL-6 and TNF-alpha, which are even better than chloroquine, a recognized antiviral and anti-inflammatory drug.
, the researchers believe their simulations and experimental data suggest that ATV and ATV/RTV could be considered for clinical trials of COVID-19.
() Reference: Natalia Fintelman-Rodrigues et al. Atazanavir res SARS-CoV-2 replication and pro-incy cytokine production. bioRixv. doi: https://doi.org/10.1101/2020.04.04.020925.