Host range of SARS-CoV-2 holds the clue for prediction of future outbreaks

Structure of SARS- CoV 2

The pandemic- COVID-19, has completed its one year since its inception from the sea food market of Wuhan, China. Till to date this has taken 2.75 million human lives all over the world. Scientists are working round the clock to come with an effective vaccine. Till to date 13 number of vaccines have been approved/ authorized. So far the scientific studies suggest the virus, SARS-CoV-2(the cause of COVID-19), likely had ancestors that originated in bats, followed by transmission to an intermediate host, and that both viruses may have an extended host range that includes primates and other mammals.

Many mammalian species host coronaviruses and these infections are frequently associated with severe clinical diseases, such as respiratory and enteric disease in pigs and cattle. Additionally, Molecular phylogenetics revealed that at least one human coronavirus (HCov-OC43) may have originated in cattle or swine and that this virus was associated with a human pandemic that emerged in the late 19th century.

Recent data suggest that coronaviruses can be transmitted from bats to other wildlife species and humans, and from humans to tigers and pigs. Hence, understanding the host range of SARS-CoV-2 and related coronaviruses is essential for improving our ability to predict and control future pandemics. It is also crucial for protecting populations of wildlife species in native habitats and under human care, particularly nonhuman primates, which may be susceptible to COVID-19. An excellent study published in the journal “Proceedings of the National Academy of Sciences of the United States of America” in August, 2020 revealed some interesting findings that support the above paragraph.

How this SARS-CoV-2 starts its journey into cells? Coronavirus entry into host cells is an important determinant of viral infectivity and pathogenesis. To enter host cells, coronaviruses first bind to a cell surface receptor for viral attachment, subsequently enter endosomes, and eventually fuse viral and lysosomal membranes. A virus surface-anchored spike protein mediates coronavirus entry. The angiotensin I converting enzyme 2 (ACE2) serves as a functional receptor for the spike protein (S) of SARS-CoV and SARS-CoV-2. Under normal physiological conditions, ACE2 is a dipeptidyl carboxypeptidase that catalyzes the conversion of angiotensin I into angiotensin 1-9, a peptide of unknown function. ACE2 also converts angiotensin II, a vasoconstrictor, into angiotensin 1-7, a vasodilator that affects the cardiovascular system and regulate other components of the renin–angiotensin system.

What is the essence of this study?

Coronaviruses may adapt to new hosts in part through mutations in S that enhance binding affinity for ACE2. The best-studied example is the evolution of SARS-CoV-like coronaviruses in the masked palm civet, which is believed to be the intermediate host for transmission of a SARS-CoV-like virus from bats to humans. The masked palm civet SARS-CoV S acquired two mutations that increased its affinity for human ACE2. Hence, to provide insights for the future zoonotic transmissions and to predict which vertebrate species could be the potential harbour of this pathogen, scientists took the help of genomics. They used a combination of comparative genomic approaches and protein structural analysis to assess the potential of ACE2 homologs from 410 vertebrate species (including representatives from all vertebrate classes: fishes, amphibians, birds, reptiles, and mammals) to serve as a receptor for SARS-CoV-2 and to understand the evolution of ACE2/SARS-CoV-2 S-binding sites. Interestingly their findings reinforced earlier findings on the natural host range of SARS-CoV-2 and predict a broader group of species that may serve as a reservoir or intermediate host(s) for this virus. Importantly, many threatened and endangered species were found to be at potential risk for SARS-CoV-2 infection based on their ACE2 binding score, suggesting that as the pandemic spreads humans could inadvertently introduce a potentially devastating new threat to these already vulnerable populations, especially the great apes and other primates. The following tables are categorized on the basis of ACE2/SARS-CoV-2 S-binding sites. This shows the risk level of species susceptible for SARS-CoV-2.

 

 

 

 

 

HIGH

Common Name

Scientific Name

IUCN Status

Human

Homo sapiens

 

Western lowland gorilla

Gorilla gorilla gorilla

CR

Northern white-cheeked gibbon

Nomascus leucogenys

CR

Sumatran orangutan

Pongo abelii

CR

Proboscis monkey

Nasalis larvatus

EN

Bonobo

Pan paniscus

EN

Chimpanzee

Pan troglodytes

EN

Red-shanked douc

Pygathrix nemaeus

EN

Golden snub-nosed monkey

Rhinopithecus roxellana

EN

Sooty mangabey

Cercocebus atys

EN

Southern pig-tailed monkey

Macaca nemestrina

VU

Rhesus monkey

Macaca mulatta

LC

Drill

Mandrillus leucophaeus

EN

 

 

 

 

 

 

 

 

 

 

MEDIUM

Common Name

Scientific Name

IUCN Status

Aye-aye

Daubentonia madagascariensis

EN

Syrian hamster

Mesocricetus auratus

VU

Sperm whale

Physeter catodon

VU

Barbary sheep

Ammotragus lervia

VU

Bison

Bison bison bison

NT

Hirola

Beatragus hunteri

CR

Wild yak

Bos mutus

Domesticated

Wild goat

Capra aegagrus

NT

Masai giraffe

Giraffa tippelskirchi

EN

Nilgiri tahr

Hemitragus hylocrius

EN

Sunda clouded leopard

Neofelis diardi

VU

Jaguar

Panthera onca

NT

Leopard 

Panthera pardus

VU

Siberian tiger

Panthera tigris altaica

EN

Cheetah

Acinonyx jubatus

VU

Hippopotamus

Hippopotamus amphibius

VU

Dama gazelle

Nanger dama

CR

European rabbit

Oryctolagus cuniculus

EN

 

 

 

 

 

 

LOW

Common Name

Scientific Name

IUCN Status

Southern white rhinoceros

Ceratotherium simum simum

NT

Black rhinoceros

Diceros bicornis

CR

Giant panda

Ailuropoda melanoleuca

VU

Wild Bactrian camel

Camelus ferus

CR

Polar bear

Ursus maritimus

VU

Bush dog

Speothos venaticus

NT

Brownhead whale

Balaena mysticetus

LC

African elephant

Loxodonta africana

VU

Straw coloured fruit bat

Eidolon helvum

NT

Large flying fox

Pteropus vampyrus

NT

Patagonian mara

Dolichotis patagonum

NT

Gray mouse lemur

Microcebus murinus

LC

Analysis of this study

Out of 401 vertebrate species taken into consideration in this study, 103 species that scored very high, high, and medium for ACE2/SARS-CoV-2 S binding, 41 (40%) are classified in one of three “threatened” categories (vulnerable, endangered, and critically endangered) on the International Union of Conservation of Nature (IUCN) Red List of Threatened Species, five are classified as near threatened, and two species are classified as extinct in the wild. For example in Cetacea, 12 of 14 species score as high, and of those two are threatened. Toothed whales have potential for viral outbreaks and have lost function of a gene that is key to the antiviral response in other mammalian lineages. If they are susceptible to SARS-CoV-2, human-to-animal transmission could pose a risk through sewage outfall and contaminated refuse from cities, commercial vessels, and cruise liners.

Conclusion

Although this in silico studies suggest potential susceptibility of diverse species, verification of infection potential is required, using cell cultures, stem cells, organoids, and other methods that do not require direct animal infection studies. Zoos and other facilities that maintain living animal collections are in a position to provide such samples for generating crucial research resources by banking tissues and cryo-banking viable cell cultures in support of these efforts.

References

1) Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates, Damaset al., Proceedings of the National Academy of Sciences of the United States of America, August, 2020.https://doi.org/10.1073/pnas.2010146117. 2)https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker

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