Covid-19: A Multi-Host Pandemic

SARS-CoV-2, the causal agent of the COVID-19 pandemic, is related to a group of viruses (Sarbecovirus) that circulate in horseshoe bats. Its origin is still uncertain, as there is lack of an identifiable intermediate host species for the proximal animal ancestor of SARS-CoV-2. Irrespective of its origin, SARS-CoV-2 has been shown to replicate in many mammalian species. So far, over forty species have been found to be susceptible to SARS-CoV-2 infection, and natural infections have been documented in at least 23 species of distant mammalian orders, including Primata, Rodentia, Carnivora, and Arthiodactyla. In two of those species, minks and white tailed deer, continued transmission among conspecifics occurred following introduction of SARS-CoV-2 from humans, at a rate which makes mink farms and deer populations suitable compartments where the virus may be maintained and evolve, and then perhaps spill back to humans or other animals as a new variant, as suggested by molecular evidence. Considering the above, what is truly unique about this pandemic, and adds a major obstacle to attain its control, is its multi-host nature. This is another compelling example of the relevance of the 'One Health' approach. This approach recognizes the inextricable links between people and nature, and visualizes the health and disease phenomenon from an integrative perspective. The COVID-19 pandemic urges us to acknowledge the interconnection between people and the remaining forms of life, and with the environments they share, and demonstrates that the improvement of global health needs a collaborative, multisectoral, and transdisciplinary approach, acting at the local, regional and global levels. This concept becomes paramount when taking into account that most diseases affecting humans in the last decades -not only COVID-19 - have been caused by pathogens originated in animals.Copyright © 2023

Human coronaviruses in the 'One Health' context

Seven human coronaviruses have been identified so far: four seasonal coronaviruses (HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1) and three novel coronaviruses (SARS-CoV, MERS-CoV, SARS-CoV-2). While seasonal coronaviruses cause only mild symptoms, novel coronaviruses cause severe and potentially fatal infections. All known coronaviruses originated in animals. Bats are considered as an origin for the majority of coronaviruses capable of infecting humans;however, rodents are proposed as natural hosts for HCoV-OC43 and HCoV-HKU1. Different animal species could serve as intermediate hosts including alpacas (HCoV-229E), livestock (HCoV-OC43), civet cats (SARS-CoV), camels (MERS-CoV), and pangolins (SARS-CoV-2). In Croatia, SARS-CoV-2 was detected in humans, pet animals, wildlife, and the environment. The COVID-19 pandemic has highlighted the role of the 'One Health' approach in the surveillance of zoonotic diseases.Copyright © 2022, University Hospital of Infectious Diseases. All rights reserved.

In silico analysis of ACE2 from different animal species provides new insights into SARS-CoV-2 species spillover.

Aim: This study aimed to analyze the phylogenetic relationships between the ACE2 of humans and other animals and investigate the potential interaction between SARS-CoV-2 RBD and ACE2 of different species. Materials & methods: The phylogenetic construction and molecular interactions were assessed using computational models. Results & conclusion: Despite the evolutionary distance, 11 species had a perfect fit for the interaction between their ACE2 and SARS-CoV-2 RBD (Chinchilla lanigera, Neovison vison, Rhinolophus sinicus, Emballonura alecto, Saccopteryx bilineata, Numida meleagris). Among them, the avian N. meleagris was reported for the first time in this study as a probable SARS-CoV-2 host due to the strong molecular interactions. Therefore, predicting potential hosts for SARS-CoV-2 for understanding the epidemiological cycle and proposal of surveillance strategies.

Here, computational analysis was employed to predict the interaction between the Spike protein from SARS-COV-2 with the ACE2 receptor with animals that could serve as a reservoir for SARS-CoV-2 spillover. Our results reported for the first time that N. meleagris could act as a possible host for SARS-CoV-2.

COVID-19 Pandemic: Current Scenario, Challenges and Future Perspectives

Background: The new public health emergency of COVID-19 caused by a novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which originated in Wuhan, Hubei province, China in December 2019, evolved into a pandemic in no time and is still in progression. The novel virus mainly targets the lower respiratory system, leading to viral pneumonia, with other associated complications of multi organ failure. Discussion(s): The bats, in particular Rhinolophus affinis, is a natural host of SARS-CoV-2 and the virus is considered to have spread to humans through yet controversial intermediate host pangolins. The incubation period ranges from 2-14 days and mode of person-to-person transmission is primari-ly via the direct contact with the infected person or through the droplets generated by the infected person during coughing or sneezing. The initiation of the infection process by SARS-CoV-2 virus is the invasion of lung type II alveolar cells via a receptor protein called angiotensin-converting enzyme 2 (ACE2) present on the cell membrane with glycosylated spike (S) viral protein that medi-ates host cell invasion. The main diagnostic tools employed are molecular methods based on nucleic acid detection engaging real-time quantitative polymerase chain reaction (RT-qPCR) and a new immunoassays based on antibodies IgM/IgG. Conclusion(s): Due to the lack of specific clinically approved anticovid-19 drugs or vaccines that could be used for its prevention or treatment, the current management approach is essentially sup-portive and symptomatic. The precautionary measures like, social distancing, cleaning hands with soap or sanitizers, using disinfectant solutions to decontaminate the surfaces of things and proper ventilation, wearing masks and other protective gears to curb transmission. The knowledge regard-ing COVID-19 therapies is still evolving and collaborative efforts are being put in to discover definitive therapies on different themes in the form of vaccines, repurposing drugs, RNA interfer-ence, docking studies, etc.Copyright © 2021 Bentham Science Publishers.

Coronavirus Pandemic: Role of Bats And Zoonotic Transmission in Humans

Background: In the past two decades, the human coronavirus (HCoV) outbreaks have gripped the international communities almost six times in different forms [HCoV-OC43 (2001);HCoV-NL63 (2004);SARS-CoV (2003);HCoV HKU1 (2005);MERS-CoV (2012);SARS-CoV--2 (2019)]. These emerging pathogens have been proven very challenging from medical perspec-tives, economic conditions, and psychological impact on human society. Introduction: SARS-CoV-2, a novel coronavirus, has evidenced a historic yet troublesome pandemic across the globe. In humans, its clinical manifestations may range from asymptomatic, severe pneumonia to mortality. Bats are the natural reservoirs of a variety of viruses belonging to the family Coronaviridae. Most of the bats harboring coronaviruses mainly reside in Asian and African regions. Objective(s): The objective was to describe the various characteristic features of all coronaviruses, clinical manifestations, and complications associated with SARS-CoV-2. The major goal was to highlight the involvement of the strong immune system of bats in the cross-species transmission of coronaviruses in intermediate hosts and, finally, zoonotic transmission in humans. Methodology: A systematic literature search was conducted for high quality research and review ar-ticles. We searched the databases for articles published between the year 1972 to 2020 with search terms zoonosis, coronaviruses, zoonotic transmissions, clinical manifestations, and the immune system of bats. Conclusion(s): The domestic and non-domestic animals come in closer contact with humans. Some requisite measures should be taken to decrease the contact with livestock to prevent further threatening viral transmissions. Furthermore, the remarkable immune system of bats is required to in-quire thoroughly to develop novel therapeutics to conquer the evolving coronaviruses in the future.Copyright © 2021 Bentham Science Publishers.

Might SARS-CoV-2 Have Arisen via Serial Passage through an Animal Host or Cell Culture?: A potential explanation for much of the novel coronavirus' distinctive genome.

Despite claims from prominent scientists that SARS-CoV-2 indubitably emerged naturally, the etiology of this novel coronavirus remains a pressing and open question: Without knowing the true nature of a disease, it is impossible for clinicians to appropriately shape their care, for policy-makers to correctly gauge the nature and extent of the threat, and for the public to appropriately modify their behavior. Unless the intermediate host necessary for completing a natural zoonotic jump is identified, the dual-use gain-of-function research practice of viral serial passage should be considered a viable route by which the novel coronavirus arose. The practice of serial passage mimics a natural zoonotic jump, and offers explanations for SARS-CoV-2's distinctive spike-protein region and its unexpectedly high affinity for angiotensin converting enzyme (ACE2), as well as the notable polybasic furin cleavage site within it. Additional molecular clues raise further questions, all of which warrant full investigation into the novel coronavirus's origins and a re-examination of the risks and rewards of dual-use gain-of-function research.

No Evidence for the Presence of SARS-CoV-2 in Bank Voles and Other Rodents in Germany, 2020-2022.

Rodentia is the most speciose mammalian order, found across the globe, with some species occurring in close proximity to humans. Furthermore, rodents are known hosts for a variety of zoonotic pathogens. Among other animal species, rodents came into focus when the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) spread through human populations across the globe, initially as laboratory animals to study the viral pathogenesis and to test countermeasures. Under experimental conditions, some rodent species including several cricetid species are susceptible to SARS-CoV-2 infection and a few of them can transmit the virus to conspecifics. To investigate whether SARS-CoV-2 is also spreading in wild rodent populations in Germany, we serologically tested samples of free-ranging bank voles (Myodes glareolus, n = 694), common voles (Microtus arvalis, n = 2), house mice (Mus musculus, n = 27), brown or Norway rats (Rattus norvegicus, n = 97) and Apodemus species (n = 8) for antibodies against the virus. The samples were collected from 2020 to 2022 in seven German federal states. All but one sample tested negative by a multispecies ELISA based on the receptor-binding domain (RBD) of SARS-CoV-2. The remaining sample, from a common vole collected in 2021, was within the inconclusive range of the RBD-ELISA, but this result could not be confirmed by a surrogate virus neutralization test as the sample gave a negative result in this test. These results indicate that SARS-CoV-2 has not become highly prevalent in wild rodent populations in Germany.

Role of the Pangolin in Origin of SARS-CoV-2: An Evolutionary Perspective.

After the recent emergence of SARS-CoV-2 infection, unanswered questions remain related to its evolutionary history, path of transmission or divergence and role of recombination. There is emerging evidence on amino acid substitutions occurring in key residues of the receptor-binding domain of the spike glycoprotein in coronavirus isolates from bat and pangolins. In this article, we summarize our current knowledge on the origin of SARS-CoV-2. We also analyze the host ACE2-interacting residues of the receptor-binding domain of spike glycoprotein in SARS-CoV-2 isolates from bats, and compare it to pangolin SARS-CoV-2 isolates collected from Guangdong province (GD Pangolin-CoV) and Guangxi autonomous regions (GX Pangolin-CoV) of South China. Based on our comparative analysis, we support the view that the Guangdong Pangolins are the intermediate hosts that adapted the SARS-CoV-2 and represented a significant evolutionary link in the path of transmission of SARS-CoV-2 virus. We also discuss the role of intermediate hosts in the origin of Omicron.

Variation in synonymous nucleotide composition among genomes of sarbecoviruses and consequences for the origin of COVID-19.

The subgenus Sarbecovirus includes two human viruses, SARS-CoV and SARS-CoV-2, respectively responsible for the SARS epidemic and COVID-19 pandemic, as well as many bat viruses and two pangolin viruses. Here, the synonymous nucleotide composition (SNC) of Sarbecovirus genomes was analysed by examining third codon-positions, dinucleotides, and degenerate codons. The results show evidence for the eight following groups: (i) SARS-CoV related coronaviruses (SCoVrC including many bat viruses from China), (ii) SARS-CoV-2 related coronaviruses (SCoV2rC; including five bat viruses from Cambodia, Thailand and Yunnan), (iii) pangolin sarbecoviruses, (iv) three bat sarbecoviruses showing evidence of recombination between SCoVrC and SCoV2rC genomes, (v) two highly divergent bat sarbecoviruses from Yunnan, (vi) the bat sarbecovirus from Japan, (vii) the bat sarbecovirus from Bulgaria, and (viii) the bat sarbecovirus from Kenya. All these groups can be diagnosed by specific nucleotide compositional features except the one concerned by recombination between SCoVrC and SCoV2rC. In particular, SCoV2rC genomes have less cytosines and more uracils at third codon-positions than other sarbecoviruses, whereas the genomes of pangolin sarbecoviruses show more adenines at third codon-positions. I suggest that taxonomic differences in the imbalanced nucleotide pools available in host cells during viral replication can explain the eight groups of SNC here detected among Sarbecovirus genomes. A related effect due to hibernating bats and their latitudinal distribution is also discussed. I conclude that the two independent host switches from Rhinolophus bats to pangolins resulted in convergent mutational constraints and that SARS-CoV-2 emerged directly from a horseshoe bat sarbecovirus.

An Update of Pharmacological and Non-pharmacological Therapies for COVID-19 Pandemic Trivia

Background: The whole planet is facing one of the scariest pandemic situations in this era. On 11th February, 2020 the World Health Organization announced the name of an unknown disease as COVID-19, which is caused by the ssRNA virus SARS-CoV-2 (formally recognized as a sister of SARS-CoV and MERS-CoV). The epicenter of this disease is Wuhan, Hubei Province, China. COVID-19 can affect all age groups, but particularly affects immune compromised and aged persons with co-morbid conditions. It is highly contagious disease that involves mild to severe respiratory symptoms along with breathing difficulties. Objectives: As SARS-CoV-2 is a new strain of β-coronavirus that spreads from animals to humans via an unknown intermediate host, no vaccines have been developed yet and only supportive treatment is given to the infected patients. The review paper highlights the pharmacological therapy as a supportive treatment given to the COVID-19 patients and nonpharmacological therapeutic approaches for the prevention. Methods: Methods: Authors were surveyed and reviewed numerous articles, magazines, news papers, conference proceedings from different search engines and made the review successful. Results: Some drugs of different categories are approved and prescribed to the patients and some others are still under investigation and have gone through clinical trials. Conclusion: As no specific treatment or drugs for this disease have been developed till the date;therefore, social distancing, home quarantine, and proper healthy lifestyle management are the best current short-term options to avoid further spread of this pervasive virus.

Major bat-borne zoonotic viral epidemics in Asia and Africa: A systematic review and meta-analysis.

Bats are the natural reservoir host for many pathogenic and non-pathogenic viruses, potentially spilling over to humans and domestic animals directly or via an intermediate host. The ongoing COVID-19 pandemic is the continuation of virus spillover events that have taken place over the last few decades, particularly in Asia and Africa. Therefore, these bat-associated epidemics provide a significant number of hints, including respiratory cellular tropism, more intense susceptibility to these cell types, and overall likely to become a pandemic for the next spillover. In this systematic review, we analysed data to insight, through bat-originated spillover in Asia and Africa. We used STATA/IC-13 software for descriptive statistics and meta-analysis. The random effect of meta-analysis showed that the pooled estimates of case fatality rates of bat-originated viral zoonotic diseases were higher in Africa (61.06%, 95%CI: 50.26 to 71.85, l2 % = 97.3, p < 0.001). Moreover, estimates of case fatality rates were higher in Ebola (61.06%; 95%CI: 50.26 to 71.85, l2 % = 97.3, p < 0.001) followed by Nipah (55.19%; 95%CI: 39.29 to 71.09, l2 % = 94.2, p < 0.001), MERS (18.49%; 95%CI: 8.19 to 28.76, l2 % = 95.4, p < 0.001) and SARS (10.86%; 95%CI: 6.02 to 15.71, l2 % = 85.7, p < 0.001) with the overall case fatality rates of 29.86 (95%CI: 29.97 to 48.58, l2 % = 99.0, p < 0.001). Bat-originated viruses have caused several outbreaks of deadly diseases, including Nipah, Ebola, SARS and MERS in Asia and Africa in a sequential fashion. Nipah virus emerged first in Malaysia, but later, periodic outbreaks were noticed in Bangladesh and India. Similarly, the Ebola virus was detected in the African continent with neurological disorders in humans, like Nipah, seen in the Asian region. Two important coronaviruses, MERS and SARS, were introduced, both with the potential to infect respiratory passages. This paper explores the dimension of spillover events within and/or between bat-human and the epidemiological risk factors, which may lead to another pandemic occurring. Further, these processes enhance the bat-originated virus, which utilises an intermediate host to jump into human species.

The pig as an amplifying host for new and emerging zoonotic viruses.

Pig production is a rapidly growing segment of the global livestock sector, especially in Asia and Africa. Expansion and intensification of pig production has resulted in significant changes to traditional pig husbandry practices leading to an environment conducive to increased emergence and spread of infectious diseases. These include a number of zoonotic viruses including influenza, Japanese encephalitis, Nipah and coronaviruses. Pigs are known to independently facilitate the creation of novel reassortant influenza A virus strains, capable of causing pandemics. Moreover, pigs play a role in the amplification of Japanese encephalitis virus, transmitted by mosquito vectors found in areas inhabited by over half the world's human population. Furthermore, pigs acted as an amplifying host in the first and still most severe outbreak of Nipah virus in Malaysia, that necessitated the culling over 1 million pigs. Finally, novel porcine coronaviruses are being discovered in high pig-density countries which have pandemic potential. In this review, we discuss the role that pigs play as intermediate/amplifying hosts for zoonotic viruses with pandemic potential and consider how multivalent vaccination of pigs could in turn safeguard human health.

Identifying the Zoonotic Origin of SARS-CoV-2 by Modeling the Binding Affinity between the Spike Receptor-Binding Domain and Host ACE2.

Despite considerable research progress on SARS-CoV-2, the direct zoonotic origin (intermediate host) of the virus remains ambiguous. The most definitive approach to identify the intermediate host would be the detection of SARS-CoV-2-like coronaviruses in wild animals. However, due to the high number of animal species, it is not feasible to screen all the species in the laboratory. Given that binding to ACE2 proteins is the first step for the coronaviruses to invade host cells, we propose a computational pipeline to identify potential intermediate hosts of SARS-CoV-2 by modeling the binding affinity between the Spike receptor-binding domain (RBD) and host ACE2. Using this pipeline, we systematically examined 285 ACE2 variants from mammals, birds, fish, reptiles, and amphibians, and found that the binding energies calculated for the modeled Spike-RBD/ACE2 complex structures correlated closely with the effectiveness of animal infection as determined by multiple experimental data sets. Built on the optimized binding affinity cutoff, we suggest a set of 96 mammals, including 48 experimentally investigated ones, which are permissive to SARS-CoV-2, with candidates from primates, rodents, and carnivores at the highest risk of infection. Overall, this work not only suggests a limited range of potential intermediate SARS-CoV-2 hosts for further experimental investigation, but also, more importantly, it proposes a new structure-based approach to general zoonotic origin and susceptibility analyses that are critical for human infectious disease control and wildlife protection.

Zoonotic and Reverse Zoonotic Transmissibility of SARS-CoV-2.

The Coronavirus Disease 2019 (COVID-19) is the first known pandemic caused by a coronavirus. Its causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), appears to be capable of infecting different mammalian species. Recent detections of this virus in pet, zoo, wild, and farm animals have compelled inquiry regarding the zoonotic (animal-to-human) and reverse zoonotic (human-to-animal) transmissibility of SARS-CoV-2 with the potential of COVID-19 pandemic evolving into a panzootic. It is important to monitor the global spread of disease and to assess the significance of genomic changes to support prevention and control efforts during a pandemic. An understanding of the SARS-CoV-2 epidemiology provides opportunities to prevent the risk of repeated re-infection of humans and requires a robust One Health-based investigation. This review paper describes the known properties and the existing gaps in scientific knowledge about the zoonotic and reverse zoonotic transmissibility of the novel virus SARS-CoV-2 and the COVID-19 disease it causes.

Application of a novel mathematical model to identify intermediate hosts of SARS-CoV-2.

Intermediate host species provide a crucial link in the emergence of zoonotic infectious diseases, serving as a population where an emerging pathogen can mutate to become human-transmissible. Identifying such species is thus a key component of predicting and possibly mitigating future epidemics. Despite this importance, intermediate host species have not been investigated in much detail, and have generally only been identified by testing for the presence of pathogens in multiple candidate species. In this paper, we present a mathematical model able to identify likely intermediate host species for emerging zoonoses based on ecological data for the candidates and epidemiological data for the pathogen. Since coronaviruses frequently emerge through intermediate host species and, at the time of writing, pose an urgent pandemic threat, we apply the model to the three emerging coronaviruses of the twenty-first century, accurately predicting palm civets as intermediate hosts for SARS-CoV-1 and dromedary camels as intermediate hosts for MERS. Further, we suggest mink, pangolins, and ferrets as intermediate host species for SARS-CoV-2. With the capacity to evaluate intermediate host likelihood among different species, researchers can focus testing for possible infection sources and interventions more effectively.

Exploration of hosts and transmission traits for SARS-CoV-2 based on the k-mer natural vector.

A severe respiratory pneumonia COVID-19 has raged all over the world, and a coronavirus named SARS-CoV-2 is blamed for this global pandemic. Despite intensive research into the origins of the COVID-19 pandemic, the evolutionary history of its agent SARS-CoV-2 remains unclear, which is vital to control the pandemic and prevent another round of outbreak. Coronaviruses are highly recombinogenic, which are not well handled with alignment-based method. In addition, deletions have been found in the genomes of several SARS-CoV-2, which cannot be resolved with current phylogenetic methods. Therefore, the k-mer natural vector is proposed to explore hosts and transmission traits for SARS-CoV-2 using strict phylogenetic reconstruction. SARS-CoV-2 clustering with bat-origin coronaviruses strongly suggests bats to be the natural reservoir of SARS-CoV-2. By building bat-to-human transmission route, pangolin is identified as an intermediate host, and civet is predicted as a possible candidate. We speculate that SARS-CoV-2 undergoes cross-species recombination between bat and pangolin coronaviruses. This study also demonstrates transmission mode and features of SARS-CoV-2 in the COVID-19 pandemic when it broke out early around the world.

An update on the origin of SARS-CoV-2: Despite closest identity, bat (RaTG13) and pangolin derived coronaviruses varied in the critical binding site and O-linked glycan residues.

The initial cases of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) occurred in Wuhan, China, in December 2019 and swept the world by 23 June 2020 with 8 993 659 active cases, 469 587 deaths across 216 countries, areas or territories. This strongly implies global transmission occurred before the lockdown of China. However, the initial source's transmission routes of SARS-CoV-2 remain obscure and controversial. Research data suggest bat (RaTG13) and pangolin carried CoV were the proximal source of SARS-CoV-2. In this study, we used systematic phylogenetic analysis of Coronavirinae subfamily along with wild type human SARS-CoV, MERS-CoV, and SARS-CoV-2 strains. The key residues of the receptor-binding domain (RBD) and O-linked glycan were compared. SARS-CoV-2 strains were clustered with RaTG13 (97.41% identity), Pangolin-CoV (92.22% identity) and Bat-SL-CoV (80.36% identity), forms a new clade-2 in lineage B of beta-CoV. The alignments of RBD contact residues to ACE2 justified? Those SARS-CoV-2 strains sequences were 100% identical by each other, significantly varied in RaTG13 and pangolin-CoV. SARS-CoV-2 has a polybasic cleavage site with an inserted sequence of PRRA compared to RaTG13 and only PRR to pangolin. Only serine (Ser) in pangolin and both threonine (Thr) and serine (Ser) O-linked glycans were seen in RaTG13, suggesting that a detailed study needed in pangolin (Manis javanica) and bat (Rhinolophus affinis) related CoV.

SARS-CoV-2 Infections in Animals: Reservoirs for Reverse Zoonosis and Models for Study.

The recent SARS-CoV-2 pandemic has brought many questions over the origin of the virus, the threat it poses to animals both in the wild and captivity, and the risks of a permanent viral reservoir developing in animals. Animal experiments have shown that a variety of animals can become infected with the virus. While coronaviruses have been known to infect animals for decades, the true intermediate host of the virus has not been identified, with no cases of SARS-CoV-2 in wild animals. The screening of wild, farmed, and domesticated animals is necessary to help us understand the virus and its origins and prevent future outbreaks of both COVID-19 and other diseases. There is intriguing evidence that farmed mink infections (acquired from humans) have led to infection of other farm workers in turn, with a recent outbreak of a mink variant in humans in Denmark. A thorough examination of the current knowledge and evidence of the ability of SARS-CoV-2 to infect different animal species is therefore vital to evaluate the threat of animal to human transmission and reverse zoonosis.