APA 7: TWs Editor & ChatGPT. (2023, October 31). Pre-Emerging Bat Coronavirus Isolated and Neutralized with Existing Medication, Scientists Report. PerEXP Teamworks. [News Link]
In a pioneering set of experiments conducted by a collective team of researchers from various U.S. research institutions, they not only detected a “pre-emerging bat coronavirus” but also showcased the potent neutralization of this virus by a readily available monoclonal antibody. Moreover, the scientists observed that commonly used antiviral drugs displayed effectiveness against the virus in in vitro tests.
The particular bat-derived coronavirus under investigation bears the name BtCoV-422. Researchers utilized a pre-existing neutralizing monoclonal antibody called mAb JC57-11, initially designed to combat the Middle East respiratory syndrome coronavirus (MERS-CoV), which has been available for an extended period. MERS-CoV is a zoonotic virus originating from bats and infecting dromedary camels, which subsequently transmit the virus to humans. Notably, BtCoV-422 shares a genetic resemblance with MERS-CoV.
Published in Science Translational Medicine, researchers from Saint Louis University in Missouri collaborated with a nationwide team of scientists. They highlighted a seemingly straightforward concept: the countermeasures that have proven effective against other coronaviruses like MERS-CoV and SARS-CoV-2 should also have an impact on BtCoV-422. While most MERS-CoV–neutralizing monoclonal antibodies exhibited limited effectiveness against the virus, mAb JC57-11 demonstrated a robust and highly effective response.
Experts emphasize the vital importance of readiness to prevent future pandemics. One of the key objectives of the World Health Organization is to recognize potential pandemic viruses and establish proactive strategies to mitigate and contain outbreaks before they can gain momentum.
Throughout the 21st century, new coronaviruses have sporadically crossed into human populations, including SARS CoV-1 in 2002, MERS-CoV in 2012, and SARS-CoV-2 in 2019. The World Health Organization’s experts have foreseen the potential for the emergence of additional coronaviruses in the near future.
Dr. Longping V. Tse, a molecular virologist at Saint Louis University, emphasized the necessity of comprehensive therapeutics and identifying conserved epitope targets for designing effective countermeasures in response to the recurring appearance of zoonotic human betacoronaviruses. He highlighted the urgency of determining the epitope, the specific part of the suspect viruses that the human immune system identifies. Furthermore, he emphasized the ongoing significance of addressing Middle East respiratory syndrome–related coronaviruses as a critical component of global health preparedness.
Bats, being Earth’s sole flying mammals, serve as hosts to a wide spectrum of viruses that do not harm them. These viruses include Ebola, Marburg, Nipah, and various coronaviruses. Researchers attribute the bats’ ability to tolerate these otherwise deadly pathogens to their extraordinary immune system. Bats exhibit longer lifespans compared to other animals of similar size, possess strong defenses against most infectious agents, and are rarely afflicted by cancer.
Tse, the lead author of the new research, pointed out that bats play a crucial role as a reservoir for numerous viruses that contribute to the transfer of coronaviruses to other mammals, including humans. He also noted that a MERS-like coronavirus has been discovered in pangolins, highlighting the broad host range of MERS-like coronaviruses. Similar to BtCoV-422, the pangolin-specific MERS-like coronavirus is regarded as a pre-emerging virus.
A) They presented the Gold-standard Fourier shell correlation (GSFSC) curve and angular distribution plot, which were generated during the global refinement of the BtCoV-422 spike bound to JC57-11 Fab using cryoSPARC v4.0.1.
B) The FSC curve and angular distribution plot were associated with the focused refinement process.
C) Color-coded representations of local resolution were provided for both the global and focused reconstructions. The top section displayed local resolution for the global reconstruction, while the bottom section showed it for the focused reconstruction.
D) The figures showed a map resulting from the focused refinement, with distinct components highlighted: the RBD (Colored blue), an N-linked glycan from the N-terminal domain (NTD) of the neighboring protomer (Colored green), the JC57-11 heavy chain (Colored yellow), and the JC57-11 light chain (Colored tan). Detailed views of the binding interface and their corresponding maps were also presented. Notably, oxygen atoms were represented in red, nitrogen atoms in blue, and sulfur atoms in yellow.
(Science Translational Medicine)
In a study published in Science Translational Medicine, Tse and his team conducted experiments to examine BtCoV-422. Their analysis revealed that BtCoV-422 shares a genetic sequence similarity of 65% with the receptor binding domain of MERS-CoV. MERS-CoV is a highly contagious coronavirus associated with a human fatality rate of 34.4%, as reported by the U.S. National Institutes of Health.
The research group examined BtCoV-422’s adaptation mechanisms by studying its capacity to interact with the entry receptor called DPP4. DPP4 is a protein located on the surface of mammalian cells and acts as the gateway through which BtCoV-422 gains access to the interior of the cell, initiating the infection process.
In contrast, SARS-CoV-2 utilizes a distinct entry route, entering cells through the ACE-2 receptor. On the other hand, BtCoV-422 employs the DPP4 receptor to access the cells of various species, including humans, as discovered by Tse and his team.
Although the identification of BtCoV-422 is significant, the virus does not currently pose a threat. Tse emphasized that “Further mutation-driven evolution would be required” would be necessary for BtCoV-422 to acquire the capability to infect humans, as stated in his research.
While the notion of limited threat may provide some comfort, it’s important to note that the virus has demonstrated efficient utilization of the DPP4 receptor. In his research, Tse and his team evaluated BtCoV-422’s replication capabilities in various human cells, including airway epithelial cells, lung fibroblasts, and lung endothelial cells.
Researchers discovered that BtCoV-422 exhibited effective replication in primary human airway cells, lung endothelial cells, and fibroblast cells, albeit with lower efficiency compared to MERS-CoV.
Tse further explained, “We also examined the effectiveness of existing countermeasures, which encompassed antiviral drugs, vaccine-elicited murine serum, and monoclonal antibodies.” The antiviral drugs evaluated included Remdesivir, Paxlovid, and Lagevrio, which is an investigational nucleoside analog medication currently deployed for the treatment of mild to moderate COVID-19.
In the laboratory setting, all these countermeasures exhibited strong inhibitory effects against BtCoV-422. However, serum obtained from mice vaccinated with an mRNA vaccine for MERS-CoV displayed diminished neutralizing activity against BtCoV-422.
Tse summarized the research focus as an exploration of BtCoV-422’s ability to infect human airway cultures relevant in a clinical context, and the evaluation of potential antiviral agents and antibodies against this virus.
Resources
- NEWSPAPER Ricks, D. (2023, October 30). Scientists isolate “pre-emerging” bat coronavirus but also identify existing medication that potently neutralizes it. Medical Xpress. [Medical Xpress]
- JOURNAL Tse, L. V., Hou, Y. J., McFadden, E., Re, L., Scobey, T., Leist, S. R., Martinez, D. R., Meganck, R. M., Schäfer, A., Yount, B., Mascenik, T., Powers, J. M., Randell, S. H., Zhang, Y., Wang, L., Mascola, J. R., McLellan, J. S., & Baric, R. S. (2023). A MERS-CoV antibody neutralizes a pre-emerging group 2c bat coronavirus. Science Translational Medicine, 15(715). [Science Translational Medicine]
