SARS-CoV-2 Pseudoparticle Infection in Mink Can Be Blocked With Endocytosis Inhibitors

Recently, Ann Song from the University of California, Riverside, and colleagues have found that SARS-CoV-2 pseudoparticle infection can be blocked in mink with the use of an endocytosis inhibitor. This could help prevent spillback of the mink population’s infection into humans. In this study, the researchers’ goal was to discover how mink become infected with SARS-CoV-2 and to identify drugs that can prevent infection. The results of this study are also among the first to investigate SARS-CoV-2 transmission in nonhumans.

First, Ms Song and colleagues aligned the amino acid sequences of ACE2 and TMPRSS2 from the mink and other species they found in databases. Then, they compared the human sequence to the mink’s overall sequence identity, residues from the ACE2–virus binding interface, and the catalytic domain in TMPRSS2. The authors found that 15 of 16 ACE2 amino acid orthologs in mink had more than 80% sequence similarity with human ACE2; however, mink TMPRSS2 was missing many of the key residues. After some cell processing, they generated human SARS-CoV-2 pseudoparticles, preincubated mink fetal cells with TMPRSS2 inhibitors or endocytosis inhibitors, and then infected the fetal mink cells with the human SARS-CoV-2 pseudoparticles.

The mink fetal cells had a 67.49% transduction efficiency for infection with the pseudoparticles, with a 0.3 multiplicity of infection, indicating that the mink cells were highly susceptible to infection with human SARS-CoV-2 pseudoparticles. Using TMPRSS2 inhibitors to reduce infection in the mink fetal cells proved no more effective than using dimethyl sulfoxide (DMSO) control. However, three endocytosis inhibitors reduced infection compared to the DMSO control, with one inhibitor showing a significant reduction.

Although COVID-19 is mostly under control for the human population, it is important to address the potential for zoonotic transmission. Many animals are still getting infected with SARS-CoV-2, which might cause the mutation of variants that could spill back into humans. Understanding that SARS-CoV-2 uses the endocytic pathway to enter nonhuman animals could be important in developing additional vaccines or blockers of viral entry for nonhuman animals and humans alike, the authors suggested.

“The data from our mink study could reduce the risk of continued transmission between animals and humans and prevent the development of more dangerous variants,” Ms Song and colleagues concluded.

Reference: 

Song A, Phandthong R, Talbot P.  Endocytosis inhibitors block SARS-CoV-2 pseudoparticle infection of mink lung epithelium. Front Microbiol. 2023;14. doi:10.3389/fmicb.2023.1258975.