Cell Science & Molecular Biology - Juniper Publishers
Abstract
The world has witnessed severe recurrent outbreaks of
highly infectious human diseases caused by deadly coronaviruses such as
severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East
respiratory syndrome coronavirus (MERS-CoV) and novel coronavirus
(2019-nCoV). Compared to the previous incidence of coronavirus diseases,
the ongoing outbreak of COVID-19 caused by 2019-nCoV is more severe,
spreading rapidly all over the globe and has been declared as a pandemic
by WHO. Previously, SARS-CoV and MERS-CoV was reported to have
originated from their natural ecological reservoir i.e. bats, and then
passed to humans through intermediate hosts palm civets and camels,
respectively. While many reports suggest the bat origin of 2019-nCoV,
but substantial evidence for animals as intermediate hosts is still
lacking. Understanding of how a virus from a reservoir adapts to new
host (s) is essential for disease management. The present review
provides the latest results on animal hosts of human coronaviruses. As
the new coronavirus is rapidly spreading around the world, future
research should aim to investigate for the next potential coronavirus
animal hosts.
Keywords: COVID-19, 2019-nCoV, SARS-CoV, MERS-CoV, Intermediate host, Pandemic
Introduction
The world is now facing a massive emergency due to
the biggest ongoing outbreak of COVID-19 caused by a highly infectious
and pathogenic novel coronavirus designated as severe acute respiratory
syndrome coronavirus 2 (2019-nCoV). The virus emerged in Wuhan, China in
December, 2019 and eventually spread all over the countries to become
pandemic as declared by WHO. There is no drug developed yet for
COVID-19, but innovative research on development of specific drug
primarily based on the knowledge of viral association with host receptor
(Ace2) by its spike protein is expanding in many countries [1]. Bats
are thought to be the source of 2019-nCoV which transmitted to humans
possibly through another animal as intermediate host [2].
Like 2019-nCoV, Ebola, Sars, Nipah viruses are also
believed to have reached humans from their probable natural reservoir,
the bats. In November 2002, a viral respiratory disease that led to the
first major pandemic of the new millennium originated from southern
China and crossed the boundaries of other countries, with over 8,000
confirmed cases at the end of June 2003, with a mortality rate of ∼9.6%
[3]. The etiologic agent of this respiratory disease identified as
SARS-CoV was found to be a betacoronavirus of bat origin that adapted to
infect the intermediate host palm civet and finally jumped into humans
[3]. A decade after the SARS-CoV outbreak, in June 2012, MERS-CoV,
emerged in Saudi Arabia, causing similar respiratory disease as SARS
[3]. In comparison to SARS-CoV, human-to-human transmission was
considered limited, but two major outbreaks in 2012 (Saudi Arabia) and
2015 (South Korea) occurred with more than 2000 cases (mortality rate of
∼35%), globally. Like SARS-CoV, MERS-CoV was found to have originated
from bats, whereas unlike SARS-CoV, it was adapted to
dromedary camels as intermediate hosts [3].
During the SARS outbreak, raccoon dogs (Nyctereutes
procyonoides) and masked palm civet (Paguma larvata) were
identified to carry SARS-CoV like viruses, before the virus was
detected in bamboo bats (Tylonycteris pachypusa and Pipistrellus
sp.). Until recently, civets are considered as a “bypass” reservoir
and the immediate zoonotic source of SARS-CoV in the Guangdong
SARS outbreak [4]. The emergence of MERS-CoV, has identified
dromedary camels as a potential intermediate host and also
indicated the mode of zoonotic transmission from camels to
humans via three possible ways: organs, flesh, and discharges
such as faeces and camel milk, since serum evidences revealed
that butchers and shepherds have higher infection rates than
individuals in other occupations [5]. Alpacas, centrally housed
with camels were also identified with MERS-CoV and it was further
observed that the MERS-CoV effectively interacts with alpaca-
DPP4 (dipeptidyl peptidase 4, receptor of MERS-CoV) followed by
infection. Though the role of alpacas is not clear in the MERS-CoV
outbreak, but it can be hypothesised that the increasing export of
alpacas might have handsome contribution in increasing the risk
of 2012 outbreak [5].
Not only SARS-CoV and MERS-CoV, several coronaviruses like
HCoV-NL63, HcoV-229E and a majority of alphacoronaviruses and
betacoronaviruses, also found to have originated from diverse
bat species, whereas HCoVOC43 and HcoV-HKU1 likely to have
originated in rodents [6]. Compared to the outbreak from these
viruses, the recent outbreak of 2019-nCoV has become so severe
that the world is now under complete lockdown. Global confirmed
cases as of today stands 3,015,298 with 207,933 fatalities [7].
Despite the severity and fatality associated with the repeated
outbreak of such diseases, coronavirus vaccines and antiviral
drugs are not yet available. The animal model that mimics human
disease is thus of an urgent need. Several studies showed that
2019-nCoV shares 96.2% amino acid sequence similarity (taking
all the ORFs) with coronavirus isolated from bats and likewise bats
are considered to be the natural source of 2019-nCoV [8]. Apart
from bats, snakes were thought to be the source or intermediate
host of 2019-nCoV but further investigation obliterated the
probability [9]. The high sequence similarity (99%) of 2019-nCoV
with the coronavirus isolated from pangolin and the presence
of typical novel coronavirus granules observed in the animal,
suggested pangolin to be the potential intermediate host of the
2019-nCoV [10]. Recently Xuhua Xia [11] has even claimed the
dogs to be an intermediate host of 2019-nCoV. Though adequate
evidences have proved the animal origin of 2019-nCoV, the natural
and intermediate host is still under question. To gain insight into
the animal reservoirs of 2019-nCoV and animal management
for COVID19 control, Shi et al. [12] evaluated the susceptibility
of different animals including model laboratory animals with
intranasal application of SARS-CoV-2. From quantification of viral
RNA by qPCR and virus titration in Vero E6 cells, it was concluded
that 2019-nCoV replicates efficiently in ferrets, but poorly in dogs,
pigs, chickens, and ducks. In contrast, many researchers point to
its transition to human through an animal such as pig. One report
pointed to snakes, for which bats are food [13]. As a natural reservoir of coronavirus, a search for the presence
of SARS-CoV, MERS-CoV and 2019-nCoV in bats, concluded that
there is no contradiction for bats being the source of these viruses
which apparently passes on to humans via an intermediate animal
host. Recently, coronaviruses similar to 2019-nCoV were reported
from Rousettus spp. and Pteropus spp of bat in India [14].
In this global pandemic situation, caused by 2019-nCoV,
though the intermediate host is still unidentified, several reports
for animals getting infected suggest inter-species transmission,
which significantly raise the risk of rapid dissemination and
infection among wild animals as well as humans. Recently, a cat
in Belgium, two dogs in Hong Kong, and five tigers, eight wild
cats and three lions in the Bronx Zoo, New York, were found to
have Covid19 disease [15,16] Also, two pet cats in New York
were tested positive for the new coronavirus
(https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/sa_one_health/sars-covanimals- us).
Previous study with related virus, SARS-CoV showed that cats can be infected and pass it on other cats [17].
(https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/sa_one_health/sars-covanimals- us).
Previous study with related virus, SARS-CoV showed that cats can be infected and pass it on other cats [17].
It appears that 2019-nCoV may infect a number of domestic
and wild animals, however, which animal(s) acts as intermediate
host for transmission of the virus in human is still unclear. It
also remains a question whether a single strain of 2019-nCoV is
capable of infecting different animals or mutational consequence
of 2019-nCoV while residing in human expands the host range.
Since cats, dogs and other animals are in close contact with
humans, emphasis should thus be given to frequent surveillance for 2019-nCoV perhaps or evaluation of their susceptibility to
any new coronavirus so that appropriate precautionary measure
can be taken before the onset of any severe devastating outbreak
causing economic, social and political disruption. The major
reason for the emergence of deadly animal viruses like 2019-nCoV
perhaps lies in the destruction of natural habitat of wild animals,
it is something like ‘throwing stones at a beehive’, so let us pay
respect to wild animals.
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