ATN-161, a small pentapeptide ɑ5β1 integrin inhibitor, has several properties that make it potentially attractive as a novel SARS-CoV-2 therapy. It is safe and well tolerated with no dose-limiting toxicity as per phase I cancer clinical trials . K18-hACE c57BL/6 J mice were inoculated with either saline or SARS-CoV-2 via intranasal administration. Post inoculation, one group of infected mice received ATN-161 (1 mg/kg), while the other received saline. The viral copy number, SARS-CoV2 gene expression, SARS-CoV2 antigen detection and histological studies of the lungs were carried out. The results were compared between infected mice with and without ATN-161 therapy.
ATN-161-treated mice had lower Genomic-N viral load in lungs than saline treated SARS-CoV-2-infected mice. Visual inspection of Genomic-N and sgm-N graph revealed that there heterogeneity among the ATN-161 treated groups, suggesting a dichotomy in this population with regards to ATN-161 treatment response and viral load, and a general trend towards reduced viral load among all ATN-161 treated groups. Morphological changes observed in infected lungs of K18- hACE2 mice included multifocal lesions, moderate interstitial pneumonia, infiltration of lymphocytes, and fibrin exudation. These were less or completely absent in infected mice with ATN-161 as well as absent in uninfected saline/ATN-161 treated mice. Moreover, ATN-161 treatment also inhibited SARS-CoV-2-induced integrin α5, and integrin αv which is responsible for the entry of SARS-CoV2 in the host cell in the K18- hACE2 mice lungs.
Thus, it can be concluded that post-infection treatment with ATN-161 reduces lung viral load, replication, improves lung histology and reduces lung α5 and αv integrin expression in a majority of SARS-CoV-2 infected k-18 mice. ATN-161 is a potential anti-COVID-19 agent and further studies are needed for better understanding.
Source: Life Sciences
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