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The evolutionary history of ACE2 usage within the coronavirus subgenus Sarbecovirus

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6 years ago

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Phylogenetic tree of the RNA-dependent RNA polymerase (RdRp) gene (nsp12) and associated geographic origin and host species. Source: Wells et al., 2021. The evolutionary history of ACE2 usage within the coronavirus subgenus Sarbecovirus
Phylogenetic tree of the RNA-dependent RNA polymerase (RdRp) gene (nsp12) and associated geographic origin and host species. Source: Wells et al., 2021. The evolutionary history of ACE2 usage within the coronavirus subgenus Sarbecovirus

Abstract

Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and SARS-CoV-2 are not phylogenetically closely related; however, both use the angiotensin-converting enzyme 2 (ACE2) receptor in humans for cell entry. This is not a universal sarbecovirus trait; for example, many known sarbecoviruses related to SARS-CoV-1 have two deletions in the receptor binding domain of the spike protein that render them incapable of using human ACE2. Here, we report three sequences of a novel sarbecovirus from Rwanda and Uganda that are phylogenetically intermediate to SARS-CoV-1 and SARS-CoV-2 and demonstrate via in vitro studies that they are also unable to utilize human ACE2. Furthermore, we show that the observed pattern of ACE2 usage among sarbecoviruses is best explained by recombination not of SARS-CoV-2, but of SARS-CoV-1 and its relatives.We show that the lineage that includes SARS-CoV-2 is most likely the ancestral ACE2-using lineage, and that recombination with at least one virus from this group conferred ACE2 usage to the lineage including SARS-CoV-1 at some time in the past. We argue that alternative scenarios such as convergent evolution are much less parsimonious; we show that biogeography and patterns of host tropism support the plausibility of a recombination scenario, and we propose a competitive release hypothesis to explain how this recombination event could have occurred and why it is evolutionarily advantageous. The findings provide important insights into the natural history of ACE2 usage for both SARS-CoV-1 and SARS-CoV-2 and a greater understanding of the evolutionary mechanisms that shape zoonotic potential of coronaviruses. This study also underscores the need for increased surveillance for sarbecoviruses in southwestern China, where most ACE2-using viruses have been found to date, as well as other regions such as Africa, where these viruses have only recently been discovered.

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Mark Wamai

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CARTA Fellow Tamale on Building Systems, Shaping Policy and Transforming Lives beyond the PhD

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3 weeks ago

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October 6, 2026

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Dr. Andrew Tamale, College of Veterinary Medicine, Animal Resources and BioSecurity (CoVAB), Makerere University, Kampala Uganda, East Africa. Photo. CARTA.

A PhD can spark impact that extends far beyond academia. Meet CARTA graduate Andrew Tamale, whose journey demonstrates the multiplier effect of research capacity strengthening—from helping transform doctoral training and generating evidence that informed safer fish consumption practices, to strengthening One Health approaches for outbreak preparedness in Uganda and beyond. 

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Source: CARTA News & Updates Issue 105

Mark Wamai

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CARTA Fellow Anywar Appointed UTANA Subject Matter Expert, Talks Medicinal Plants

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3 weeks ago

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October 6, 2026

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Dr. Godwin Anywar, Department of Plant Sciences, Microbiology and Biotechnology, College of Natural Sciences (CoNAS), Makerere University. Kampala Uganda, East Africa.

Godwin Anywar, cohort 6, Makerere University, was appointed as a Subject Matter Expert on the Manuscript Technical Evaluators team of the Uganda Textbook Academic and Non-Fiction Authors Association (UTANA) on August 31, 2026. In this role, Godwin will contribute to the qualitative, academic, and pedagogical assessment of manuscripts submitted under the Capacity Building for School Books Project (CB-SP). The four-year project, implemented jointly with the Department of Teacher Education and Training Development (TETD) of Uganda’s Ministry of Education and Sports (MoES), aims to strengthen authorship and support the development of school books in Uganda’s education sector.

He was also featured in Uganda’s New Vision on July 26, 2026, in a special report on Uganda’s medicinal plants.

Source: CARTA News & Updates Issue 105

Mark Wamai

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Makerere Hosts TERID Hub Early Career Researchers Grant Writing Workshop

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3 weeks ago

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October 6, 2026

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The Emerging and Re-emerging Infectious Diseases (TERID) Hub continued its efforts to strengthen the capacity of 17 early career researchers (ECRs) (10 men, 7 women) on an institutional level by holding a grant writing workshop from September 8 - 11, 2026, at Makerere University, Kampala Uganda, East Africa.

The Emerging and Re-emerging Infectious Diseases (TERID) Hub continued its efforts to strengthen the capacity of early career researchers (ECRs) on an institutional level by holding a grant writing workshop from September 8 – 11, 2026, at Makerere University. The workshop, attended by 17 ECRs (10 men, 7 women), strengthened participating researchers’ capacity by equipping them with critical skills to secure competitive funding. The intensive sessions bridged the gap between innovative academic concepts and fundable proposals, focusing heavily on decoding complex funder criteria and structuring compelling narratives. Participants prioritized the CONNECT-VAX call, which closely aligns with the Hub’s core work, and formed two groups: one on vaccine research and development capacity, the other on public trust and demand for vaccines manufactured in Africa.

Through this call, the Hub engaged collaborators from West Africa (Sierra Leone) and East Africa (Kenya and Tanzania) in developing two of its grant applications. Individual concepts on leishmaniasis, leptospirosis, tuberculosis, and pharmaceutical inventory management were also advanced, bringing the total to eight proposals across four funding calls, including Makerere University Research and Innovation Fund (MAK-RIF 8), Wellcome, and WHO/TDR.

To date, the Hub’s grant writing effort has attracted over USD 700,000. The workshop reinforced the Hub’s commitment to mentoring early-career researchers and championing research in emerging and re-emerging infectious diseases.

Source: CARTA News & Updates Issue 105

Mark Wamai

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