[Q&A] Bats, Pangolins and the Coronavirus

While bats have been put forward as the original host of SARS-CoV-2 nonetheless, the transmission of the virus from bats to humans requires intermediate hosts as well. Several studies have linked pangolins with SARS-CoV-2 infection where coronaviruses found in pangolin are highly similar to the novel coronavirus, which suggests that the mammal is the most likely intermediate host. Prof Dr Abdul Rahman Omar, Dean Faculty of Veterinary Medicine, Universiti Putra Malaysia, however, warns that further study needs to be carried out to identify additional intermediate hosts.

Q&A

Have we found similar viruses in our Malayan pangolins as well?

“So far, there is no study on the detection of coronaviruses in Malayan pangolins (Manis javanica) in Malaysia. A previous study done by Chinese researchers has detected viruses from different family namely the Coronavirus and Paramyxovirus in pangolins. The study indicates these viruses are potentially pathogenic in pangolin and can affect the respiratory and intestinal tracts of the pangolins.”

A recent metagenomic sequencing study of samples collected from pangolins in China has identified pangolin-associated coronaviruses that share 91% similarity to SARS-CoV-2. These pangolin-associated coronaviruses belong to two sub-lineages of SARS-CoV-2 virus. One of the sub-lineages exhibits high similarity to SARS-CoV-2 in the receptor-binding domain (RBD) of the Spike (S) protein. These findings show that pangolin is the most likely intermediate host of SARS-CoV-2, however, further study needs to be carried out to identify additional intermediate hosts.” 

Can you tell us the similarities and differences in the coronaviruses found in pangolins and SARS-CoV-2? 

“Currently, we only know the genomic information of the pangolins coronavirus and SARS-CoV-2. The pangolin-associated coronaviruses share 91 % whole-genome sequence similarity to SARS-CoV-2, where the coronaviruses in pangolin represent two sub-lineages of SARS-CoV-2. One of the sublineages exhibit high similarity (97 %) to the receptor-binding domain (RBD) of the Spike (S) protein of SARS-CoV-2. It is interesting to note that the pangolin coronavirus and SARS-CoV-2 share identical amino acids at the first five key RBD residues. Meanwhile, the rest of the SARS-CoV-2 genome is closely related to bat coronavirus (RaTG13 virus) isolated from bat Rhinolophus affinis, and pangolin coronavirus (Pangolin/1), with ∼96% and ∼ 91% overall genome sequences identity, respectively. Overall these findings suggest the convergent and cross-species evolution of SARS-like virus in bats and pangolins that brought out the emergence of SARS-CoV-2.”

Are they as dangerous as SARS-CoV-2? Do they also infect human beings?

“The study that identified novel coronavirus is from sick and dead pangolins that also harbour other viruses including virus of the member of the paramyxovirus namely Sendai virus which is a known pathogen that affects the respiratory tract of mice, hamsters, guinea pigs, rats, and occasionally pigs and bats. Because of the lack of healthy pangolins as a control, the study could not determine whether the lesions detected at the respiratory and intestinal tracts are due to Sendai virus and/or coronavirus. Hence, it is difficult to confirm that the coronavirus is pathogenic and can cause fatal infection to pangolins.

In addition, there is no direct evidence that the coronavirus from pangolins can infect human. Currently, the cross-species transmission of pangolin coronavirus to human is not known, whether it can happen directly or it requires an additional intermediate host. Further study needs to be carried out to resolve this. However, based on the high similarity of the pangolin coronavirus and SARS-CoV-2, there is a possibility that the virus can infect human.”

Where or how could these pangolins pick up such viruses and how did horseshoe bats come into play?

“Bats seem to be the primary host (natural reservoir) while pangolin as the intermediate host of SARS-CoV-2. The high sequence similarity of coronaviruses of bats and pangolin indicate the cross-species transmission of coronavirus between these animals. The sharing of coronaviruses in bats, pangolins and possibly in other animal species may lead to the emergence of novel viruses of divergent or recombinant viruses origin with the potential threat to infect human.”

Do we also have the similar bat species here in Malaysia? 

“A study has reported more than 100 bat species in Peninsular Malaysia including the horseshoe bat of Rhinolophus genus. However, the study on the detection of viruses in bats in Malaysia is limited. Nevertheless, many novel coronaviruses have been discovered in a variety of bat species throughout the world in Asia, Europe, Africa, and America. Most SARS and SARS-like coronaviruses were discovered in bats genus Rhinolophus from China and in some parts of Europe, while novel beta-coronaviruses related to SARS-CoV have been detected in bats of Hipposideros and Chaerophon species from Kenya and Nigeria.”

Could you explain the possible transmission between the coronavirus from both the pangolins and bats to humans?

“The cross-species (interspecies) transmission between animals before the virus jump to human is not well understood. A simplified diagram showing the cross-species transmission of the virus from the natural host, bats to the intermediate host, pangolin and possibly to other wildlife animals are shown below. The figure also shows the cross-species transmission of viruses in the emergence of other deadly zoonotic coronavirus infection in human, SARS-CoV and MERS-CoV. 

Since bats are the natural host, they harbour over 200 coronaviruses. More importantly, the horseshoe bat (genus Rhinolophus) is the reservoir for a large number of viruses that have a close genetic relationship with the coronavirus associated with SARS. Hence, bats are the mixing vessels of different coronaviruses from other animals. The mixing of viruses between bats and the intermediate hosts will lead to the emergence of novel viruses. These novel coronaviruses may harbour genetic characteristic that gives the ability to the virus to infect other animals including human hence causing zoonotic spillover.

In the case of COVID-19, the SARS-Cov-2 acquire to the ability to bind to a cellular receptor, angiotensin-converting enzyme 2 (ACE2) of mammals including bats and humans. Besides, the SARS-CoV-2 bind tightly to the human ACE2 receptor hence, explaining the reason why the COVID-19 virus can easily infect human and sustain an efficient human to human transmission leading to the current pandemic that we are witnessing.”

With the findings of coronavirus in pangolins, how does this helps us in developing a vaccine for COVID-19? 

“Detection of coronavirus in pangolins may help in controlling the spread of this virus in animals. Further study needs to be carried out to determine the role of pangolin in the emergence of SARS-CoV-2 and to identify additional intermediate host that will help in controlling the spread of this virus among animals.”

What is the latest development from your team in understanding the coronavirus better?

“Our group has been working on coronaviruses of animal origin namely from chickens, cats and pigs. Most of our studies are focused towards understanding the viruses better in terms of their genetic features, pathogenesis and immunology. Chicken coronavirus commonly known as infectious bronchitis virus (IBV) is an economic importance disease affecting poultry. Our group has successfully developed vaccines against IBV using local virus strain. Using some of this information we are working together with researchers from the medical side in developing a vaccine against COVID-19.

Although cats possess low risk to transmit the virus to human, they are susceptible to SARS-CoV-2 infection. Hence, our group is studying the risk of cats in the transmission of COVID-19, besides, to detect the virus in cats by using serology and molecular techniques. So far there is no report of COVID-19 virus in cats in Malaysia. Detection of the COVID-19 virus in cats will be confirmed by sequencing study besides to characterize the genetic changes of the virus isolated from these naturally infected cats.”

While pangolins are an endangered species, there is still a demand, especially in Traditional Chinese Medicine (TCM). What is your advice for people consuming pangolin with the latest development of SARS-CoV-2?

“I urge the public to stop buying wildlife and exotic animals as food delicacy and using them as part of the TCM since any activity related to hunting, farming, movement and selling of wildlife and exotic animals as food sources may potentially contribute to the emergence of new viruses of public health concern. Malaysia has a strict law in any activity related to wildlife animals. However, the legislation that regulates wildlife farming and trade varies from countries to countries. Total banning may not be a realistic way to reduce the risk, especially in poorer regions of the world where it can be an important food source.”

What is the major lesson learned from SARS and now COVID-19 in terms of the emergence of zoonotic diseases?

“It has been well established that bats are the reservoir for many dangerous viral diseases such as Nipah, Hendra, Ebola, and Marburg. We know now that bats also play an important role in the coronavirus zoonotic spillover with the emergence of SARS-CoV (2003), MERS-CoV (2012) and COVID-19 (2019). Since SARS-CoV and COVID-19 viruses were first detected from wet-markets that sell various animals including wild animals, identifying the animals could help control the outbreaks.

Wet-markets selling live and dead animals namely dogs, chickens, pigs, snakes, civets, bats, and more are common sites in China and other countries in South East Asia, put humans and animals in constant close contact. This place is the hotspot for the emergence of novel viruses since it facilitates the virus to jump from animal to human. Hence, any unauthorized activity that increases the human contact with wildlife animals during hunting, farming, movement and selling of live animal markets should not be allowed. 

Coronavirus zoonotic spillover requires several factors to align, including the ecological, epidemiological and behavioural determinants of the virus exposure, and the within-human factors that affect susceptibility to infection. As the human population expands, deforestation, increase in farming activities, and societal changes occur, human contact with wildlife will continue to increase. This increases the risk that emerging zoonotic viruses, including coronaviruses, pose to human and animal health. Surveillance combined with scientific studies to better understand zoonotic animal coronaviruses and spillover will enable us to stay a step ahead of the next epidemic.”

**All previous posts about COVID-19 here: https://sciencemediacentremalaysia.com/tag/covid-19/