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The evolutionary history of ACE2 usage within the coronavirus subgenus Sarbecovirus

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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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Health

New Tools for Paediatric Evaluation of Disability Inventory in Children developed

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Dr. Angelina Kakooza, Associate Professor in the Department of Paediatrics, School of Medicine, College of Health Sciences (CHS), Makerere University.

Dr. Angelina Kakooza an Associate Professor in the Department of Paediatrics, School of Medicine, College of Health Sciences (CHS) conducted a study to adapt the Paediatric Evaluation of Disability Inventory (PEDI) for Uganda. The PEDI was originally developed and standardized to measure functional performance in American children. The study performed by Prof. Kakooza and the research team is the first of its kind conducted in sub-Saharan Africa. The study describes the adaptation, translation, and validation process undertaken to develop a culturally relevant PEDI for Uganda (PEDI‐UG).

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Provider perspectives on the acceptability & tolerability of dolutegravir-based anti-retroviral therapy after national roll-out in Uganda: A qualitative study

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Henry Zakumumpa delivers a lecture in 2014. Photo credit: UNDP Uganda

The World Health Organization recommends dolutegravir (DTG) as the for first-line and second-line antiretroviral therapy (ART) worldwide. However, little is known about the acceptability and tolerability of DTG-based ART at routine points-of-care in Uganda. Henry Zakumumpa (Cohort Four Graduate, Makerere University) in the BMC Infectious Diseases, set out to explore the perceptions of clinicians in ART clinics regarding the acceptability and tolerability of DTG-based ART since national roll-out in March 2018 in Uganda.

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Source: CARTA Newsletter Issue 47

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Call For Applications: Merck Foundation Africa Research Summit 2022

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A screenshot of the 4th Winner of the Merck Best African Woman Researcher Award, Maria Nabaggala of the Infectious Diseases Institute (IDI), Makerere University. Source: Merck Foundation

MERCK FOUNDATION AFRICA RESEARCH SUMMIT – MARS 2022 will be held in Dubai with THE AIM TO EMPOWER WOMEN AND YOUTH IN RESEARCH.

MARS 2022 will have scientific support from African Union Scientific, Technical and Research Commission (AU-STRC), Infectious Diseases Institute, College of Health Sciences, Makerere University, Kenya Medical Research Institute (KEMRI) Graduate School, Advanced Center for Treatment, Research and Education in Cancer (ACTREC), India and Merck Foundation.

The annual summit aims to contribute to building research capacity in the African research community, with special focus on “THE ROLE OF SCIENTIFIC RESEARCH IN RESPONDING TO CANCER AND VACCINES DEVELOPMENT – TWO EMERGING CHALLENGES IN AFRICA”.

On other note the organizing committee will present the “BEST YOUNG AFRICAN RESEARCHER AWARD” and the “BEST AFRICAN WOMAN RESEARCHER AWARD” to recognize the outstanding contribution of African Female Scientists with the aim to promote women in research and advance their contribution to STEM (Science, Technology, Engineering and Mathematics).

The annual Summit -MARS will open a discussion with Ministries of Health, Education, Information, Science and Technology and Gender from across Africa to define policies with the aim to empower women and youth in STEM and to address the vital role of research in the improvement and sustainable development of population’s health with specific emphasis on
how to translate knowledge into action – the ‘know-do gap’ – to improve health and make an impact on society.

The summit will be a unique opportunity for the winners of MARS RESEARCH AWARDS to share their research output and findings. It is also an opportunity for networking and career development. The Summit will provide a platform where they will be able to discuss and enable a conducive environment for better research during the ministerial panel that will be conducted on the 15th of November, 2022.

ABSTRACT SUBMISSION DETAILS

Abstracts are invited from final year African PhD students and young investigators involved in research related to either of the following topics:

  • Cancer (specially in women)
  • Vaccines Development

All applicants should be primarily based at African research Institutes and Universities, although collaboration within Africa as well as outside is encouraged.

DEADLINE: 31ST July, 2022


APPLY NOW

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Send your abstracts to: MARS[at]MERCK-FOUNDATION.COM

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Merck Foundation, together we can make a difference.

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