Covid Animal Vault-19 Can Cause A New Round of Human Diseases

Watch out for dogs (and cats too)

A new variant of SARS-CoV-2 lurks beneath the streets of New York City.recently paper Smith et al. SARS-CoV-2 samples were extracted from 14 wastewater treatment facilities in the city. The team has developed a method for detecting mutations in important regions of the genome that are the receptor-binding domains of peplomers.

As expected, they found various Covid-19 variants in the sample, including alpha, beta, delta, and gamma. They also discovered four different “mysterious” strains, WNY1, 2, 3, and 4 from three wastewater sites. These four mysterious mutants have surprisingly nasty consequences. The receptor-binding domain RNA extracted from the sample contained up to 29. Mutations in 4 variants detected (some previously observed in variants of concern or interest, others specific to these samples) Figure 1 shows the mutations found in many other variants. Shows duplication. Among the 3.5 million sequences found in the GISAIDSARS-CoV-2 database.

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All of the mutations shown in Figure 1 occur in small regions of the viral genome sampled by sewer surveys. This region specifies the receptor binding domain where the virus attaches to the ACE2 receptor on the surface of the host cell. Receptor-binding domains are also targets for the majority of protective antibodies. Mutations in this area can have serious effects on transmission and immunity.

Most mysterious mutations Mutations occur between amino acid positions 437 and 508. It is part of the peaplomer that is in direct contact with the ACE2 receptor.

Extensive mutations in the receptor binding domain are functional. The authors report that pseudoviruses with receptor-binding domains replaced by potential mutant domains are infectious. This is not entirely unexpected, as polymorphisms shared with the mutants of interest enhance the function of the peplomer. Co-amino acid substitutions at positions N440, L452, and N501 enhance receptor binding affinity. Mutations at positions K417, N439, K444, N460, E484, Q493, and S494 reduce viral neutralization by convalescent sera and selected monoclonal antibodies. Obviously, amino acid substitutions at 12 new sites are feasible. This is particularly noteworthy with the deletion at position 484, a site known to interact directly with both ACE2 and neutralizing antibodies. It is important to determine the potential role of each of these mysterious mutations in immune avoidance and enhanced function. They may anticipate changes not yet seen in the new mutants of concern.

Smith et al. It is speculated that these variants originated from non-human hosts, not from human sources. The guess is based on some observations. First, the mysterious variant is only observed in some samples, but not in all samples. The authors argue that if variants are widespread in the population, they are found throughout the city and are not limited to specific sewers. Second, observation of pseudoviruses with “mysterious” receptor-binding domains can infect non-human ACE2 receptors, especially rat and mouse receptors.

Finally, we know that SARS-CoV-2 can infect many species other than pangolins and humans. Up to 40% of all dogs tested in the United States have antibodies to SARS-CoV-2. Several subspecies infect wild home and field mice. Up to 30% of all white-tailed deer in the northeast are Covid-19 antibody positive. In the early stages of the pandemic, reports of infections in both domestic and big cats kept in zoos were reported.

SARS-CoV-2, like the influenza virus, may be involved in zoonotic volleyball. Infections from animals can invade humans. The SARS-CoV-2 strain is infected with mink, which has regained its favor by infecting humans. As early as January 2021, Danish farmed mink showed signs of SARS-CoV-2 infection. These viruses were relayed to a human population and then sequenced. NS study Bayari Ormos et al. A mutation directly derived from mink zoonotic disease, the receptor-binding domain Y453F, results in up to 4-fold higher ACE2 receptor affinity, suggesting a much more contagious virus. .. In the future, we need to be aware of new subspecies emerging from the fauna that inhabit our ecosystems.

Smith et al. We investigated the resistance of pseudoviruses carrying a mutant receptor binding domain to currently approved monoclonal antibodies (etesebimab, bamuranibimab, and imdebimab). They report that WNY1 and 2 are partially neutralized by etesebimab and imdevimab. The WNY3 and 4 variants are completely resistant to all monoclonal antibodies tested. All four variants are also completely resistant to bablanivimab. Researchers also tested these mutations against naturally occurring antibodies in convalescent antisera. Convalescent sera neutralize both WNY 1 and 2, but are much less effective against WNY 3 and 4. The neutralizing titer of the serum of fully vaccinated individuals was also significantly reduced.

Smith et al. Pseudoviruses used to test antibody neutralization contain only mutations in the receptor binding domain, whereas complete variants are far more likely to significantly reduce antibody neutralization. Please note that it is expensive. They conclude that “the characteristics of these mutant strains provide them with the ability to increase their threat to human health.”

It was beneficial to see this small area of ​​the virus. Mysterious mutants display the full range of mutations that can occur within SARS-CoV-2 RNA. Receptor-binding domains show a broader degree of variability here. It symbolizes the potential for viral mutations not only in the receptor binding domain, but also in the peplomer and the rest of the viral genome, enhancing pathogenicity, vaccine and monoclonal antibody resistance, immunosuppression, and transmission. There is a possibility.

Ultimately, the extreme mutations found in the highly localized mysterious mutants of New York City are not due to zoonotic mutants, but to human populations, perhaps ward-replicating mutants. Do not add the possibility of effluent from highly regional clusters. Treatment of immunocompromised patients. Extreme fluctuations in S protein have been reported to occur in such patients. In each case, the final take-out message is that the variants documented so far are only a subset of what is expected from future SARS-CoV-2 infections.