Virus World

The main protease, Mpro (or 3CLpro) in SARS-CoV-2 is a viable drug target because of its essential role in the cleavage of the virus polypeptide. Feline infectious peritonitis, a fatal coronavirus infection in cats, was successfully treated previously with a prodrug GC376, a dipeptide-based protease inhibitor.

Here, we show the prodrug and its parent GC373, are effective inhibitors of the Mpro from both SARS-CoV and SARS-CoV-2 with IC50 values in the nanomolar range. Crystal structures of SARS-CoV-2 Mpro with these inhibitors have a covalent modification of the nucleophilic Cys145. NMR analysis reveals that inhibition proceeds via reversible formation of a hemithioacetal. GC373 and GC376 are potent inhibitors of SARS-CoV-2 replication in cell culture. They are strong drug candidates for the treatment of human coronavirus infections because they have already been successful in animals.  The work here lays the framework for their use in human trials for the treatment of COVID-19. Coronavirus main protease is essential for viral polyprotein processing and replication. Here Vuong et al. report efficient inhibition of SARS-CoV-2 replication by the dipeptide-based protease inhibitor GC376 and its parent GC373, which were originally used to treat feline coronavirus infection.

Published in Nature Commun.  (August 27, 2020):

https://doi.org/10.1038/s41467-020-18096-2

Reports of human-to-feline transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1 and of limited airborne transmission among cats2 prompted us to evaluate nasal shedding of SARS-CoV-2 from inoculated cats and the subsequent transmission of the virus by direct contact between virus-inoculated cats and cats with no previous infection with the virus. Three domestic cats were inoculated with SARS-CoV-2 on day 0. One day after inoculation, a cat with no previous SARS-CoV-2 infection was cohoused with each of the inoculated cats to assess whether transmission of the virus by direct contact would occur between the cats in each of the three pairs. Nasal and rectal swab specimens were obtained daily and immediately assessed for infectious virus on VeroE6/TMPRSS2 cells.

On day 1, we detected virus from two of the inoculated cats. By day 3, virus was detectable in all three inoculated cats, with continued detection of virus until day 5 in all cats and until day 6 in two of the three cats. The cats with no previous infection were cohoused with the inoculated cats on day 1. Two days later (day 3), one of the cats with no previous infection had infectious virus detected in a nasal swab specimen, and 5 days later, virus was detected in all three cats that were cohoused with the inoculated cats.

Published in N. England J. Medicine (May 13, 2020):

https://doi.org/10.1056/NEJMc2013400

But scientists say it’s unclear whether felines can spread the virus to people so pet-owners need not panic yet. Cats can be infected with the coronavirus that causes COVID-19 and spread it to other cats, but dogs are not really susceptible to the infection, according to researchers in China. The team, at Harbin Veterinary Research Institute in China, also concludes that chickens, pigs, and ducks are not likely to catch the virus.

Scientists say the findings are interesting, but that cat-owners should not be alarmed just yet. The results are based on lab experiments in which a small number of animals were deliberately infected with high doses of the virus, SARS-CoV-2, and do not represent real-life interactions between people and their pets, says virologist Linda Saif at The Ohio State University in Columbus. There is no direct evidence that the infected cats secreted enough coronavirus to infect people, she says. With the coronavirus spreading rapidly around the world, some have raised concerns about whether the virus can pass between pets and people. So far, there have been a few reports of pets being infected: a cat in Belgium and two dogs in Hong Kong. “Cats and dogs are in close contact with humans, and therefore it is important to understand their susceptibility to SARS-CoV-2 for COVID-19 control,” write the authors of the latest study, a preprint posted on bioRxiv on 31 March.

The team, led by virologist Bu Zhigao, infected five domestic cats with SARS-CoV-2 through the nose. When two of the cats were euthanized six days later, the researchers found viral RNA, as well as infectious virus particles, in their upper respiratory tracts. The other three infected cats were put in cages next to three uninfected felines. The team later detected viral RNA in one of the non-infected cats, which suggests that they contracted the virus from the infected cats through respiratory droplets. All four cats also produced antibodies against SARS-CoV-2. Surveillance for SARS-CoV-2 in cats should be considered as part of efforts to eliminate COVID-19 in humans, the authors note in the preprint, which has not been peer reviewed.

Preprint available in bioRxiv (March 31, 2020): 

https://doi.org/10.1101/2020.03.30.015347

Final publication appeared in Science (April 8, 2020):

https://doi.org/10.1126/science.abb7015

Cats and dogs are just as likely to be infected with SARS-CoV-2 as people are, according to a survey in northern Italy that is the largest study of pets so far. Nicola Decaro at the University of Bari and his colleagues took nose, throat or rectal swabs of 540 dogs and 277 cats in northern Italy between March and May (E. I. Patterson et al. Preprint at bioRxiv http://doi.org/d4r7; 2020). The animals lived in homes with infected people, or in regions severely affected by COVID-19.

Nicola Decaro at the University of Bari and his colleagues took nose, throat or rectal swabs of 540 dogs and 277 cats in northern Italy between March and May (E. I. Patterson et al. Preprint at bioRxiv http://doi.org/d4r7; 2020). The animals lived in homes with infected people, or in regions severely affected by COVID-19. Infection rates among cats and dogs were comparable with those among people in Europe at the time of testing, suggesting that it is not unusual for pets to be infected. The findings have not yet been peer reviewed.

Preprint available at bioRxiv (July 23, 2020):

https://doi.org/10.1101/2020.07.21.214346

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China, and rapidly spread worldwide. Previous studies suggested cat could be a potential susceptible animal of SARS-CoV-2.

Here, we investigated the infection of SARS-CoV-2 in cats by detecting specific serum antibodies. A cohort of serum samples were collected from cats in Wuhan, including 102 sampled after COVID-19 outbreak, and 39 prior to the outbreak. 15 of 102 (14.7%) cat sera collected after the outbreak were positive for the receptor binding domain (RBD) of SARS-CoV-2 by indirect enzyme linked immunosorbent assay (ELISA).

Among the positive samples, 11 had SARS-CoV-2 neutralizing antibodies with a titer ranging from 1/20 to 1/1080. No serological cross-reactivity was detected between the SARS-CoV-2 and type I or II feline infectious peritonitis virus (FIPV). Our data demonstrates that SARS-CoV-2 has infected cat population in Wuhan during the outbreak.

Preprint Available at bioRXV (April 3, 2020):

https://doi.org/10.1101/2020.04.01.021196