Research

The evolutionary history of ACE2 usage within the coronavirus subgenus Sarbecovirus

Published

4 years ago

March 29, 2021

Mark Wamai

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.

Please see Downloads for the paper

Wells-et-al.-2021.-The-evolutionary-history-of-ACE2-usage-within-the-coronavirus-subgenus-Sarbecovirus Download

Related Topics:coronavirus Denis K. Byarugaba recombination viral ecology virus evolution

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PIM CoE Magazine Issue 1: Jul-Dec 2024

Published

27 minutes ago

February 5, 2025

Betty Kyakuwa

Cover page of the Public Investment Management Center of Excellence (PIM CoE) Magazine Issue 1: July - December 2024. College of Business and Management Sciences (CoBAMS), Makerere University, Kampala Uganda, East Africa.

The Public Investment Management Center of Excellence (PIM CoE) was conceived as a result of the 2016 PIM Diagnostic study done by the World Bank and Ministry of Finance Planning and Economic Development with support from Makerere University School of Economics that discovered inefficiencies in PIM in Uganda.

This report highlights the work, achievements and prospects of the Center. The Center plans to start offering Advanced level training through Post Graduate Diploma (PGD) in PIM and Master of Science in Economic and Investment Modelling (MEIM). I am pleased to introduce this report to the public for use by all stakeholders.

I would like to appreciate PIM CoE Secretariat, partners, staff and well-wishers for technical support, daily running of the Center and their role in the realization of these achievements.

Special thanks go to Ministry of Finance, Planning and Economic Development, National Planning Authority, Cambridge Resources International (CRI) and Makerere University for the overwhelming support rendered towards the development of the Center.

Prof. Edward Bbaale
Principal & Principal Investigator, CoBAMS/PIM CoE

Makerere-CoBAMS-PIM-CoE-Magazine-Issue-1-Jul-Dec-2024 Download

Research

CARTA Graduate Dr. Drago on Advancing Research in Infectious Diseases

Published

2 days ago

February 3, 2025

Mark Wamai

Dr. Kato Charles Drago at work in the Lab. Photo: CARTA.

In our latest ‘Stories of Change’ feature, CARTA graduate, Kato Charles Drago, cohort 3, Makerere University shares his journey from an early-career scientist to a leading expert in infectious disease in Uganda. His work focuses on biomarkers for zoonotic diseases, securing over $5 million in research funding, and establishing a biosafety level 2 lab for high-impact research at Makerere. Beyond his research, Kato is mentoring the next generation of African scientists and strengthening regional collaborations.

Read the full story here

Source: CARTA Newsletter Issue 85

General

CARTA Fellow Dr. Wandera Receives Research Excellence Award

Published

2 days ago

February 3, 2025

Mark Wamai

Right to Left: Prof. James Wokadala, Prof. Edward Bbaale, Dr. Allen Kabagenyi, Dr. Stephen Ojiambo Wandera, Dr. Patricia Ndugga and Ms. Namugenyi Christabellah. Convocation Luncheon, 75th Graduation Ceremony, Day 2, CoBAMS, CHS and CoNAS. 14th January 2025, Research, Teaching, Students Excellence Awards, Edge Road, Makerere University, Kampala Uganda, East Africa.

Stephen Wandera, cohort 2, Makerere University, was nominated for the prestigious Vice Chancellor’s Research Excellence Award 2025. This nomination recognizes his outstanding contributions to research excellence. The award ceremony took place on January 14, 2025, during the Convocation luncheon, following the 75^th graduation ceremony of Makerere. We congratulate Stephen on this significant achievement and commend his dedication to advancing research within his field.

Source: CARTA Newsletter Issue 85