Evolution to increased positive charge on the viral spike protein may be part of the adaptation of SARS-CoV-2 to human transmission

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic, continues to evolve and infect individuals. The exterior surface of the SARS-CoV-2 virion is dominated by the spike protein and the current work examined spike protein biochemical features that have changed during the 2 years that SARS-CoV-2 has infected humans. These biochemical properties may influence virion survival and promote movement through the environment and within the human airway to reach target cells to bind, enter and establish the next round of infection. In addition to selective pressure to avoid immune recognition of viral proteins, we hypothesised that SARS-CoV-2 emerged from an animal reservoir capable of human infection and transmission but in a sub-optimum state and a second level of selective pressure is acting on these biochemical features. Our analysis identified a striking change in spike protein charge, from -8.3 in the original Lineage A and B viruses to -1.26 in the current Omicron viruses. In summary, we conclude that in addition to immune selection pressure, the evolution of SARS-CoV-2 has also altered viral spike protein biochemical properties. Future vaccine and therapeutic development should also exploit and target these biochemical properties.

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance.

Investment in Africa over the past year with regards to SARS-CoV-2 genotyping has led to a massive increase in the number of sequences, exceeding 100,000 genomes generated to track the pandemic on the continent. Our results show an increase in the number of African countries able to sequence within their own borders, coupled with a decrease in sequencing turnaround time. Findings from this genomic surveillance underscores the heterogeneous nature of the pandemic but we observe repeated dissemination of SARS-CoV-2 variants within the continent. Sustained investment for genomic surveillance in Africa is needed as the virus continues to evolve, particularly in the low vaccination landscape. These investments are very crucial for preparedness and response for future pathogen outbreaks. One-Sentence SummaryExpanding Africa SARS-CoV-2 sequencing capacity in a fast evolving pandemic.

A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa

The progression of the SARS-CoV-2 pandemic in Africa has so far been heterogeneous and the full impact is not yet well understood. Here, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations, predominantly from Europe, which diminished following the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1 and C.1.1. Although distorted by low sampling numbers and blind-spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a breeding ground for new variants.

Unique protein features of SARS-CoV-2 relative to other Sarbecoviruses

Defining the unique properties of SARS-CoV-2 protein sequences, has potential to explain the range of Coronavirus Disease 2019 (COVID-19) severity. To achieve this we compared proteins encoded by all Sarbecoviruses using profile Hidden Markov Model similarities to identify protein features unique to SARS-CoV-2. Consistent with previous reports, a small set of bat and pangolin-derived Sarbecoviruses show the greatest similarity to SARS-CoV-2 but unlikely to be the direct source of SARS-CoV-2. Three proteins (nsp3, spike and orf9) showed differing regions between the bat Sarbecoviruses and SARS-CoV-2 and indicate virus protein features that might have evolved to support human infection and/or transmission. Spike analysis identified all regions of the protein that have tolerated change and revealed that the current SARS-CoV-2 variants of concern (VOCs) have sampled only a fraction (~31%) of the possible spike domain changes which have occurred historically in Sarbecovirus evolution. This result emphasises the evolvability of these coronaviruses and potential for further change in virus replication and transmission properties over the coming years.

A SARS-CoV-2 lineage A variant (A.23.1) with altered spike has emerged and is dominating the current Uganda epidemic

Introductory paragraphSARS-CoV-2 genomic surveillance in Uganda provides an opportunity to provide a focused description of the virus evolution in a small landlocked East African country. Here we show a recent shift in the local epidemic with a newly emerging lineage A.23 evolving into A.23.1 which is now dominating the Uganda cases and has spread to 26 other countries. Although the precise changes in A.23.1 as it has adapted are different from the changes in the variants of concern (VOC), the evolution shows convergence on a similar set of proteins. The A.23.1 spike protein coding region has accumulated changes that resemble many of the changes seen in VOC including a change at position 613, a change in the furin cleavage site that extends the basic amino acid motif, and multiple changes in the immunogenic N-terminal domain. In addition, the A.23.1lineage encodes changes in non-spike proteins that other VOC show (nsp6, ORF8 and ORF9). The clinical impact of the A.23.1 variant is not yet clear, however it is essential to continue careful monitoring of this variant, as well as rapid assessment of the consequences of the spike protein changes for vaccine efficacy.

Alternate primers for whole-genome SARS-CoV-2 sequencing

As the world is struggling to control the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), there is an urgency to develop effective control measures. Essential information is encoded in the virus genome sequence with accurate and complete SARS-CoV-2 sequences essential for tracking the movement and evolution of the virus and for guiding efforts to develop vaccines and antiviral drugs. While there is unprecedented SARS-CoV-2 sequencing efforts globally, approximately 19 to 43% of the genomes generated monthly are gapped, reducing their information content. The current study documents the genome gap frequencies and their positions in the currently available data and provides an alternative primer set and a sequencing scheme to help improve the quality and coverage of the genomes.