Understanding the Current Debate on COVID-19 Origins: Unpacking Recent Discoveries

By Jonathan Latham, PhD and Allison Wilson, PhD

This article originally appeared as a Twitter thread, now expanded into an essay format.

In the ongoing investigation into the origins of COVID-19, many are captivated by the latest revelations regarding DEFUSE grant applications and their implications for the #covidorigin and #lableak discussions. As raised by Nicholas Wade and further analyzed by researchers like @emilyakopp and @USRTK, these findings are anything but conclusive; in fact, they heighten the mystery surrounding the origins of SARS-CoV-2.

Unraveling the Evidence

Why are these findings so puzzling? A 2022 study by Bruttel et al. identified six hallmark sites of reverse engineering within the SARS-CoV-2 genome. However, significantly, these sites account for just 0.1% or fewer of the overall genetic makeup of the virus. Thus, the question arises: if we entertain the possibility of a lab leak, where did the remainder of the genome originate? It’s a compelling area of inquiry, demanding our attention.

SARS-CoV-2 not only exhibits signs of manipulation but also presents clear evidence of evolutionary adaptation for human hosts, creating a paradox that cannot be ignored. The evolutionary narrative is further expanded upon in a recent paper by Ou et al. from July 2023, which surprisingly received little traction within the scientific community and online social spheres.

The Overlooked Study by Ou et al.

Despite its relatively low profile, Ou et al.’s study merits close scrutiny. Its authors, hailing from esteemed institutions in Beijing, explored the closest spike protein relatives of SARS-CoV-2, specifically BANAL-52 and BANAL-236. They investigated key areas like receptor binding efficiencies and protein structures, generating insights that could shift our understanding of the virus’s origins.

One striking point from their research is the receptor binding affinity of the SARS-CoV-2 spike protein, which was found to be strongest for human ACE2 receptors, followed by weaker affinities towards those from raccoon dogs and other species. This detail has intriguing implications for the potential zoonotic origins of the virus.

Investigating Binding Affinities

The study’s findings on binding affinities were particularly illuminating:

1. Finding 1: The spike protein of SARS-CoV-2 displayed the highest binding efficiency to human ACE2, while its affinity for raccoon dog ACE2 was significantly weaker. Interestingly, while SARS1 and the BANAL viruses demonstrated stronger binding to raccoon dog ACE2, SARS-CoV-2 lagged far behind.

2. Finding 2: A comprehensive analysis revealed that BANAL-52 and BANAL-236 both bound well to 14 different bat ACE2 receptors tested, while SARS-CoV-2 displayed weaker binding capabilities across the board. Notably, a single amino acid change (H498Q) was identified in SARS-CoV-2 that diminished its binding efficiency to bat ACE2.

These insights suggest that SARS-CoV-2 might not have evolved directly from bat coronaviruses as assumed by prevailing zoonosis theories, thus raising more questions about the virus’s evolutionary journey.

The Complexities of Glycan Structures

One of the most critical results highlighted by the authors involves the structural differences between the spike proteins, particularly regarding glycan attachments. SARS-CoV-2 lacks a glycan at position 370, a feature conserved among similar coronaviruses and instrumental in shielding proteins from degradation. The trade-off here seems to be between enhancing receptor binding efficiency and ensuring structural integrity in the harsh environment of the bat gastrointestinal tract.

Through detailed analysis, it was found that the glycan’s absence in SARS-CoV-2 potentially boosts its ability to infect human lungs but raises compelling questions regarding its evolutionary path. The two critical mutations necessary for SARS-CoV-2 to acquire its distinctive features suggest an intricate evolutionary landscape rather than a straightforward leak or engineering scenario.

Potential Implications for Origins and Evolution

The findings challenge our understanding of SARS-CoV-2’s journey. Evidence suggests it didn’t merely spill over from an animal but may reflect an extended period of adaptation within an unknown host, possibly a human, where the virus could evolve in response to acquired immunity. This insight aligns with our Mojiang Miner theory: the hypothesis that SARS-CoV-2 emerged from miners in southern China who contracted a mysterious illness in 2012, facilitating a unique opportunity for virus evolution.

Understanding the dynamics of the spike protein’s evolution and its host interaction sheds light on why SARS-CoV-2 might not fit neatly into the zoonosis narrative favored by many investigators. The complexity surrounding its binding afflictions and structural adaptations invites reconsideration of the existing hypotheses.

The Future of COVID-19 Origins Research

The implications of these findings suggest that the narrative of COVID-19’s origins is still unfolding. As more data emerges, including potential evidence from international collaborations and ongoing studies, a clearer picture may begin to take shape. While definitive answers remain elusive, the intricate interplays of evolution and potential engineering underscore the need for continued research and open, unbiased discourse in the scientific community.

As we move forward, staying attuned to emerging research, especially in under-explored areas, will be imperative in unraveling the true origins of SARS-CoV-2. Upcoming events such as the Society of Virology Conference shall provide platforms for sharing insights and advancing the discourse further, potentially illuminating the path ahead.

If this exploration into the complex narrative of COVID-19’s origins strikes a chord, consider sharing it with fellow enthusiasts of scientific inquiry. The quest for understanding is best pursued together.