Graphical abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an infectious disease that has spread worldwide. Current treatments are limited in both availability and efficacy, such that improving our understanding of the factors that facilitate infection is urgently needed to more effectively treat infected individuals and to curb the pandemic. We and others have previously demonstrated the significance of interactions between the SARS-CoV-2 spike protein, integrin α5β1, and human ACE2 to facilitate viral entry into host cells in vitro. We previously found that inhibition of integrin α5β1 by the clinically validated small peptide ATN-161 inhibits these spike protein interactions and cell infection in vitro. In continuation with our previous findings, here we have further evaluated the therapeutic potential of ATN-161 on SARS-CoV-2 infection in k18-hACE2 transgenic (SARS-CoV-2 susceptible) mice in vivo. We discovered that treatment with single- or repeated intravenous doses of ATN-161 (1 mg/kg) within 48 h after intranasal inoculation with SARS-CoV-2 lead to a reduction of lung viral load, viral immunofluorescence, and improved lung histology in a majority of mice 72 h post-infection. Furthermore, ATN-161 reduced SARS-CoV-2-induced increased expression of lung integrin α5 and αv (an α5-related integrin that has also been implicated in SARS-CoV-2 interactions) as well as the C–X–C motif chemokine ligand 10 ( Cxcl10 ), further supporting the potential involvement of these integrins, and the anti-inflammatory potential of ATN-161, respectively, in SARS-CoV-2 infection. To the best of our knowledge, this is the first study demonstrating the potential therapeutic efficacy of targeting integrin α5β1 in SARS-CoV-2 infection in vivo and supports the development of ATN-161 as a novel SARS-CoV-2 therapy.

No abstract

Effective measures are needed to prevent the spread and infectivity of SARS-CoV-2 that causes COVID-19. Chemical inactivation may help to prevent the spread and transmission of this and other viruses. Hence, we tested the SARS-CoV-2 antiviral activity of acetic acid, the main component of vinegar, in vitro. Inactivation and binding assays suggest that acetic acid is virucidal. We found that 6% acetic acid, a concentration typically found in white distilled vinegar, effectively inactivated SARS-CoV-2 after 15-min incubation with a complete loss of replication of competent virus as measured by TCID50. Transmission electron microscopy further demonstrated that 6% acetic acid disrupts SARS-CoV-2 virion structure. In addition, 6% acetic acid significantly inhibits and disrupts the binding of SARS-CoV-2 spike protein binding to ACE2, the primary SARS-CoV-2 cell receptor, after contact with spike protein for 5, 10, 30 and 60 minutes incubation. Taken together, our findings demonstrate that acetic acid possesses inactivating activity against SARS-CoV-2 and may represent a safe alternative to commonly used chemical disinfectants to effectively control the spread of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an infectious disease that has spread worldwide. Current treatments are limited in both availability and efficacy, such that improving our understanding of the factors that facilitate infection is urgently needed to more effectively treat infected individuals and to curb the pandemic. We and others have previously demonstrated the significance of interactions between the SARS-CoV-2 spike protein, integrin alpha5beta1 and human ACE2 to facilitate viral entry into host cells in vitro. We previously found that inhibition of integrin alpha5beta1 by the clinically validated small peptide ATN-161 inhibits these spike protein interactions and cell infection in vitro. In continuation with our previous findings, here we have further evaluated the therapeutic potential of ATN-161 on SARS-CoV-2 infection in k18-hACE2 transgenic (SARS-CoV-2 susceptible) mice in vivo. We discovered that treatment with single- or repeated intravenous doses of ATN-161 (1 mg/kg) within 48 hours after intranasal inoculation with SARS-CoV-2 lead to a reduction of lung viral load, viral immunofluorescence and improved lung histology in a majority of mice 72 hours post-infection. Furthermore, ATN-161 reduced SARS-CoV-2-induced increased expression of lung integrin alpha 5 and alpha v (an alpha 5-related integrin that has also been implicated in SARS-CoV-2 interactions) as well as the C-X-C motif chemokine ligand 10 (Cxcl10), further supporting the potential involvement of these integrins, and the anti-inflammatory potential of ATN-161, respectively, in SARS-CoV-2 infection. To the best of our knowledge, this is the first study demonstrating the potential therapeutic efficacy of targeting integrin alpha5beta1 in SARS-CoV-2 infection in vivo and supports the development of ATN-161 as a novel SARS-CoV-2 therapy.