Understanding the Complex Dynamics of Cross-Species Transmission: A Comprehensive Analysis of SARS-CoV-2 and its Potential Impact on Bovine Species

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The global impact of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has reached unprecedented levels. As of October 7, 2023, the World Health Organization (WHO) reported over 700 million confirmed cases and 6,961,014 deaths, marking a critical global public health crisis [1]. The disease manifests across a spectrum, from asymptomatic cases to severe respiratory illnesses, and its fatality rate is notably influenced by age [3,7].

Zoonotic Origin and Variant Evolution:

Severe acute respiratory SARS-CoV-2, believed to originate zoonotically from bats through intermediate hosts like raccoon dogs, has led to a myriad of variants, including alpha, beta, gamma, delta, and omicron [8-14]. The receptor-binding domain (RBD) and N-terminal domain (NTD) of the spike (S) protein are crucial genetic determinants facilitating worldwide transmission, affecting the angiotensin-converting enzyme 2 (ACE2) receptor [15,16]. Recent research indicates that omicron variant mutations, especially in the RBD region, increase the risk of cross-species transmission [20,21].

Host Receptors and Cross-Species Transmission:

Beyond ACE2, tyrosine kinase receptor UFO (AXL) and neuropilin 1 (NRP1) have emerged as potential receptors facilitating SARS-CoV-2 invasion [22-25]. These receptors play a role in cross-species transmission, a phenomenon observed in various animals. Recent studies suggest a potential link between SARS-CoV-2 and bovines, posing implications for the global food supply chain [26]. The susceptibility of bovines to SARS-CoV-2 remains underexplored, and the influencing factors for infection in bovines are not fully understood.

Zoonotic Transmission and Food Supply Implications:

Bovines, essential for meat production worldwide, face potential short-, medium-, and long-term implications due to the prevalence of COVID-19 [27,28]. Bovines can be susceptible to various coronaviruses, including bovine coronavirus (BCoV), and the zoonotic transmission of BCoVs has been reported [29,30]. The evolving nature of SARS-CoV-2 raises concerns about its potential to infect cattle, leading to outbreaks within this species.

Cross-Species Transmission Beyond Bovines:

Previous studies have shown SARS-CoV-2 transmission in various species, including hamsters, minks, rhesus monkeys, ferrets, mice, and even wild white-tailed deer [31-35]. This underscores the zoonotic potential of the virus and the need for vigilance regarding inter-species transmission.

Molecular Analysis and Transmission Potential:

Through structural and genetic analysis, it has been revealed that the S protein of SARS-CoV-2 may breach the species barrier and transmit to cattle. The interaction between bovine ACE2, AXL, NRP1, and S protein largely determines cross-species transmission potential, emphasizing the importance of understanding these molecular interactions. The study also identified critical residues in NTD and RBD of S, interacting with ACE2, AXL, and NRP1.

Discussion

The discussion aims to delve into the complexities and implications of the findings presented in the previous sections. The multifaceted landscape of emerging infectious diseases, particularly zoonotic viruses, has become a substantial threat to global public health. The text addresses various aspects, including the susceptibility of different species, potential cross-species transmission, and the molecular mechanisms underlying the interactions between SARS-CoV-2 and its receptors in bovines.

The initial focus of the discussion revolves around the threat posed by highly contagious viruses such as Influenza, HIV-1, Ebola, and the ongoing challenges with SARS-CoV-2 and the emerging monkeypox outbreak. Zoonotic diseases, highlighted by a study from Bangladesh, have been recurrent and pose a continual risk to human populations. The text emphasizes the necessity of understanding cross-species transmission, especially with livestock species like cattle, which play a crucial role in the global food supply.

The discussion then moves to the exploration of the susceptibility of cattle to SARS-CoV-2. While pigs and chickens have been deemed non-susceptible, there is ambiguity regarding cattle’s susceptibility. Studies suggest that while bovines may not be susceptible in vivo, factors like age, management, and general health must be considered. The presence of seropositive cows in Germany indicates a potential for spillover events, emphasizing the importance of studying the impact of natural SARS-CoV-2 infection on ruminant farms.

The text introduces the exploration of ACE2, AXL, and NRP1 receptors as potential entry points for SARS-CoV-2 in bovines. A comparative analysis of amino acid sequences aims to identify key residues in the binding interface between receptors and the S protein. The electrostatic potential energy map provides insights into the susceptibility of bovines to cross-species infection. The analysis extends to predicting protein tertiary structures, considering multiple species, to understand the variations in receptor-virus interactions.

The discussion then elaborates on the role of ACE2 as a potential receptor, acknowledging previous studies on mutations that may affect SARS-CoV-2 binding. However, the text presents contrasting findings regarding the susceptibility of bovine ACE2 to SARS-CoV-2, emphasizing the importance of species distinctions within Bovidae.

Moving to AXL and NRP1, the discussion suggests that these proteins might facilitate cross-species transmission. Comparative analysis with other species indicates similarities in the binding interfaces, raising concerns about the susceptibility of bovines to SARS-CoV-2.

The text further explores the impact of SARS-CoV-2 variants, specifically the delta and omicron variants, on receptor binding. Variations in key residues are identified, prompting consideration of potential changes in infectious ability and infectivity in cattle.

The discussion concludes by highlighting the significance of the findings in controlling SARS-CoV-2 infection and preventing pandemics among livestock. It emphasizes the need for further exploration of molecular mechanisms, utilizing functional experiments and in vitro/in vivo models. A comprehensive understanding of viral entry pathways and host specificity is crucial for formulating effective disease prevention and control strategies.

In summary, the discussion integrates findings from the study, addressing the intricacies of SARS-CoV-2 interactions with ACE2, AXL, and NRP1 receptors in bovines. It underscores the importance of ongoing research to enhance our understanding of cross-species transmission and guide public health interventions.


reference link : https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02222-9#Sec10

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