Virology Research in South Africa—from a Great Legacy to an Optimistic Future

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "General Virology".

Deadline for manuscript submissions: 1 December 2025 | Viewed by 20268

Special Issue Editors


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Guest Editor
Molecular Biology and Virology Research Laboratory, Department of Medical Biosciences, University of the Western Cape, Bellville 7535, South Africa
Interests: human coronaviruses; SARS-CoV; HCoV-NL63; MERS-CoV; SARS-CoV-2; molecular and cell biology
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Guest Editor
1. Department of Virology, National Health Laboratory Service, Johannesburg, South Africa
2. Faculty of Health Sciences, Division of Medical Viriology, University of Cape Town, Cape Town, South Africa
Interests: molecular biology; viral phylogenetics; respiratory viruses; influenza; RSV; SARS-CoV-2; CMV; HIV
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We recently published a Viruses Special Issue entitled “State-of-the-Art Virology Research in South Africa”, which has garnered much interest and received numerous submissions. Given the success of the previous Special Issue, we are excited to extend an invitation to our colleagues to participate in a second volume of this Special Issue. The second volume of the Special Issue of the journal Viruses will focus on “Virology Research in South Africa—from a Great Legacy to an Optimistic Future”. As a continuation of the First Volume, this volume aims to provide a comprehensive overview of research on HIV, viral hepatitis, influenza, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), coronaviruses, other less studied respiratory viruses, zoonotic viruses as well as research on viral vaccines, vaccine development and clinical trials on viral vaccines conducted in South Africa. Other areas relevant to this issue are research related to antiviral resistance for HIV and other viral drugs. This issue is not restricted to research on human viruses, and we invite submission of all virology research from South Africa. This is a great opportunity to showcase all the virus research, and new research niches, that were established due to the SARS-CoV-2 pandemic by South African researchers and their collaborators through submission of original research and review articles.

Prof. Dr. Burtram C. Fielding
Dr. Ziyaad Valley-Omar
Guest Editors

Manuscript Submission Information

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Keywords

  • SARS-CoV-2
  • other respiratory viruses
  • vaccines
  • HIV
  • antiviral resistance
  • zoonotic viruses
  • hepatitis viruses
  • enteric viruses
  • novel viruses/virus discovery

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Related Special Issue

Published Papers (7 papers)

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Research

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21 pages, 7171 KiB  
Article
In Silico Discovery and Evaluation of Inhibitors of the SARS-CoV-2 Spike Protein–HSPA8 Complex Towards Developing COVID-19 Therapeutic Drugs
by Liberty T. Navhaya, Thabe M. Matsebatlela, Mokgerwa Z. Monama and Xolani H. Makhoba
Viruses 2024, 16(11), 1726; https://doi.org/10.3390/v16111726 - 31 Oct 2024
Viewed by 1096
Abstract
The SARS-CoV-2 spike protein is pivotal in the COVID-19 virus’s life cycle, facilitating viral attachment to host cells. It is believed that targeting this viral protein could be key to developing effective COVID-19 prophylactics. Using in silico techniques, this study sought to virtually [...] Read more.
The SARS-CoV-2 spike protein is pivotal in the COVID-19 virus’s life cycle, facilitating viral attachment to host cells. It is believed that targeting this viral protein could be key to developing effective COVID-19 prophylactics. Using in silico techniques, this study sought to virtually screen for compounds from the literature that strongly bind and disrupt the stability of the HSPA8–spike protein complex. To evaluate the interactions between the individual proteins and the protein complex attained from protein–protein docking using BioLuminate, molecular docking was performed using the Maestro Schrodinger Suite. The screened small molecules met all bioavailability conditions, Lipinski’s and Veber’s rules, and the required medicinal chemistry properties. Protein–protein docking of the spike protein and HSPA8 identified the optimal pose with a PIPER cluster size of 65, a PIPER pose energy of −748.301 kcal/mol, and a PIPER pose score of −101.189 kcal/mol. Two small molecules, NSC36398 and NSC281245, showed promising docking scores against the spike protein individually and in a complex with HSPA8. NSC36398 had a docking score of −7.934 kcal/mol and a binding free energy of −39.52 kcal/mol with the viral spike protein and a docking score of −8.029 kcal/mol and binding free energy of −38.61 with the viral protein in complex with HSPA8, respectively. Mevastatin had a docking score of −5.099 kcal/mol and a binding free energy of −44.49 kcal/mol with the viral protein and a docking score of −5.285 kcal/mol and binding free energy of −36.65 kcal/mol with the viral protein in complex with HSPA8, respectively. These results, supported by extensive 2D interaction diagrams, suggest that NSC36398 and NSC281245 are potential drug candidates targeting SARS-CoV-2 spike protein. Full article
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16 pages, 2471 KiB  
Article
Patterns of HIV-1 Drug Resistance Observed Through Geospatial Analysis of Routine Diagnostic Testing in KwaZulu-Natal, South Africa
by Lilishia Gounder, Aabida Khan, Justen Manasa, Richard Lessells, Andrew Tomita, Melendhran Pillay, Sontaga C. Manyana, Subitha Govender, Kerri-Lee Francois, Pravi Moodley, Nokukhanya Msomi, Kerusha Govender, Raveen Parboosing, Sikhulile Moyo, Kogieleum Naidoo and Benjamin Chimukangara
Viruses 2024, 16(10), 1634; https://doi.org/10.3390/v16101634 - 19 Oct 2024
Viewed by 2310
Abstract
HIV-1 drug resistance (HIVDR) impedes treatment and control of HIV-1, especially in high-prevalence settings such as KwaZulu-Natal (KZN) province, South Africa. This study merged routine HIV-1 genotypic resistance test (GRT) data with Geographic Information Systems coordinates to assess patterns and geographic distribution of [...] Read more.
HIV-1 drug resistance (HIVDR) impedes treatment and control of HIV-1, especially in high-prevalence settings such as KwaZulu-Natal (KZN) province, South Africa. This study merged routine HIV-1 genotypic resistance test (GRT) data with Geographic Information Systems coordinates to assess patterns and geographic distribution of HIVDR in KZN, among ART-experienced adults with virological failure. We curated 3133 GRT records generated between 1 January 2018 and 30 June 2022, which includes the early phase of dolutegravir (DTG) rollout, of which 2735 (87.30%) had HIVDR. Of the 2735, major protease, nucleoside, and non-nucleoside reverse transcriptase inhibitor mutations were detected in 41.24%, 84.97% and 88.08% of GRTs, respectively. Additional genotyping of HIV-1 integrase for 41/3133 (1.31%) GRTs showed that 17/41 (41.46%) had integrase strand transfer inhibitor resistance. Notably, of 26 patients on DTG with integrase genotyping, 9 (34.62%) had DTG-associated resistance mutations. Dual- or triple-class resistance was observed in four of every five GRTs. The odds of HIVDR increased significantly with age, with ≥60 years having 5 times higher odds of HIVDR compared to 18–29 years (p = 0.001). We identified geospatial differences in the burden of HIVDR, providing proof of concept that this could be used for data-driven public health decision making. Ongoing real-time HIVDR surveillance is essential for evaluating the outcomes of the updated South African HIV treatment programme. Full article
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14 pages, 1486 KiB  
Article
Comparative Effects of Efavirenz and Dolutegravir on Metabolomic and Inflammatory Profiles, and Platelet Activation of People Living with HIV: A Pilot Study
by Crystal G. Roux, Shayne Mason, Louise D. V. du Toit, Jan-Gert Nel, Theresa M. Rossouw and Helen C. Steel
Viruses 2024, 16(9), 1462; https://doi.org/10.3390/v16091462 - 14 Sep 2024
Viewed by 1372
Abstract
Antiretroviral therapy (ART) has reduced the mortality and morbidity associated with HIV. However, irrespective of treatment, people living with HIV remain at a higher risk of developing non-AIDS-associated diseases. In 2019, the World Health Organization recommended the transition from efavirenz (EFV)- to dolutegravir [...] Read more.
Antiretroviral therapy (ART) has reduced the mortality and morbidity associated with HIV. However, irrespective of treatment, people living with HIV remain at a higher risk of developing non-AIDS-associated diseases. In 2019, the World Health Organization recommended the transition from efavirenz (EFV)- to dolutegravir (DTG)-based ART. Data on the impact of this transition are still limited. The current study therefore investigated the metabolic profiles, cytokine inflammatory responses, and platelet activation before and after the treatment transition. Plasma samples from nine virally suppressed adults living with HIV and sixteen healthy, HIV-uninfected individuals residing in Gauteng, South Africa were compared. Metabolite and cytokine profiles, and markers associated with platelet activation, were investigated with untargeted proton magnetic resonance metabolomics, multiplex suspension bead array immunoassays, and sandwich enzyme-linked immunosorbent assays, respectively. In those individuals with normal C-reactive protein levels, the transition to a DTG-based ART regimen resulted in decreased concentrations of acetoacetic acid, creatinine, adenosine monophosphate, 1,7-dimethylxanthine, glycolic acid, 3-hydroxybutyric acid, urea, and lysine. Moreover, increased levels of formic acid, glucose, lactic acid, myo-inositol, valine, glycolic acid, and 3-hydroxybutyric acid were observed. Notably, levels of interleukin-6, platelet-derived growth factor-BB, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor–alpha, soluble cluster of differentiation 40 ligand, as well as regulated on activation, normal T-cell expressed and secreted (RANTES) reached levels close to those observed in the healthy control participants. The elevated concentration of macrophage inflammatory protein-1 alpha was the only marker indicative of elevated levels of inflammation associated with DTG-based treatment. The transition from EFV- to DTG-based regimens therefore appears to be of potential benefit with metabolic and inflammatory markers, as well as those associated with cardiovascular disease and other chronic non-AIDS-related diseases, reaching levels similar to those observed in individuals not living with HIV. Full article
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18 pages, 1518 KiB  
Article
Outbreaks of H5N1 High Pathogenicity Avian Influenza in South Africa in 2023 Were Caused by Two Distinct Sub-Genotypes of Clade 2.3.4.4b Viruses
by Celia Abolnik, Laura Christl Roberts, Christine Strydom, Albert Snyman and David Gordon Roberts
Viruses 2024, 16(6), 896; https://doi.org/10.3390/v16060896 - 31 May 2024
Cited by 1 | Viewed by 1849
Abstract
In 2023, South Africa continued to experience sporadic cases of clade 2.3.4.4b H5N1 high-pathogenicity avian influenza (HPAI) in coastal seabirds and poultry. Active environmental surveillance determined that H5Nx, H7Nx, H9Nx, H11Nx, H6N2, and H12N2, amongst other unidentified subtypes, circulated in wild birds and [...] Read more.
In 2023, South Africa continued to experience sporadic cases of clade 2.3.4.4b H5N1 high-pathogenicity avian influenza (HPAI) in coastal seabirds and poultry. Active environmental surveillance determined that H5Nx, H7Nx, H9Nx, H11Nx, H6N2, and H12N2, amongst other unidentified subtypes, circulated in wild birds and ostriches in 2023, but that H5Nx was predominant. Genome sequencing and phylogenetic analysis of confirmed H5N1 HPAI cases determined that only two of the fifteen sub-genotypes that circulated in South Africa in 2021–2022 still persisted in 2023. Sub-genotype SA13 remained restricted to coastal seabirds, with accelerated mutations observed in the neuraminidase protein. SA15 caused the chicken outbreaks, but outbreaks in the Paardeberg and George areas, in the Western Cape province, and the Camperdown region of the KwaZulu-Natal province were unrelated to each other, implicating wild birds as the source. All SA15 viruses contained a truncation in the PB1-F2 gene, but in the Western Cape SA15 chicken viruses, PA-X was putatively expressed as a novel isoform with eight additional amino acids. South African clade 2.3.4.4b H5N1 viruses had comparatively fewer markers of virulence and pathogenicity compared to European strains, a possible reason why no spillover to mammals has occurred here yet. Full article
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9 pages, 1667 KiB  
Article
Exploring the Epidemiological Surveillance of Hepatitis A in South Africa: A 2023 Perspective
by Keveshan Bhagwandin, Jayendrie Thaver-Kleitman, Kathleen Subramoney, Morubula Jack Manamela and Nishi Prabdial-Sing
Viruses 2024, 16(6), 894; https://doi.org/10.3390/v16060894 - 31 May 2024
Viewed by 1243
Abstract
Hepatitis A (HAV) presents a significant global health concern with diverse clinical manifestations primarily transmitted through fecal–oral routes, emphasizing the critical role of sanitation and water cleanliness in transmission dynamics. Age-related variations, notably asymptomatic presentation in children, add complexity. The World Health Organization’s [...] Read more.
Hepatitis A (HAV) presents a significant global health concern with diverse clinical manifestations primarily transmitted through fecal–oral routes, emphasizing the critical role of sanitation and water cleanliness in transmission dynamics. Age-related variations, notably asymptomatic presentation in children, add complexity. The World Health Organization’s (WHO) endemicity classification aids in understanding prevalence and control strategies. This study examines 2023 South African epidemiological data on HAV cases, evaluating age distribution, incidence rates, and provincial disparities. Data from the national surveillance system and weather services were analyzed. Findings reveal distinct age-related trends, with the highest seroprevalence observed in the 5–9 age group with the most burdened areas located in the Western Cape, KwaZulu-Natal, and Gauteng provinces. Furthermore, seasonal rainfall variations correlate with increased incidence in Western Cape and KZN. The amalgamation of results suggest a potential epidemiological shift, emphasizing the need for updated immunization strategies. Noteworthy patterns, like the rise in 5–9-year-olds, may be influenced by factors such as school clustering and migration. Provincial disparities and the impact of climatic events underscore the necessity for dynamic vaccination strategies and surveillance network enhancements. This study highlights the urgency for improved understanding and response to HAV in South Africa. Full article
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Review

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35 pages, 2499 KiB  
Review
Potential Effects of Hyperglycemia on SARS-CoV-2 Entry Mechanisms in Pancreatic Beta Cells
by Tara M. Michaels, M. Faadiel Essop and Danzil E. Joseph
Viruses 2024, 16(8), 1243; https://doi.org/10.3390/v16081243 - 2 Aug 2024
Viewed by 2041
Abstract
The COVID-19 pandemic has revealed a bidirectional relationship between SARS-CoV-2 infection and diabetes mellitus. Existing evidence strongly suggests hyperglycemia as an independent risk factor for severe COVID-19, resulting in increased morbidity and mortality. Conversely, recent studies have reported new-onset diabetes following SARS-CoV-2 infection, [...] Read more.
The COVID-19 pandemic has revealed a bidirectional relationship between SARS-CoV-2 infection and diabetes mellitus. Existing evidence strongly suggests hyperglycemia as an independent risk factor for severe COVID-19, resulting in increased morbidity and mortality. Conversely, recent studies have reported new-onset diabetes following SARS-CoV-2 infection, hinting at a potential direct viral attack on pancreatic beta cells. In this review, we explore how hyperglycemia, a hallmark of diabetes, might influence SARS-CoV-2 entry and accessory proteins in pancreatic β-cells. We examine how the virus may enter and manipulate such cells, focusing on the role of the spike protein and its interaction with host receptors. Additionally, we analyze potential effects on endosomal processing and accessory proteins involved in viral infection. Our analysis suggests a complex interplay between hyperglycemia and SARS-CoV-2 in pancreatic β-cells. Understanding these mechanisms may help unlock urgent therapeutic strategies to mitigate the detrimental effects of COVID-19 in diabetic patients and unveil if the virus itself can trigger diabetes onset. Full article
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Other

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20 pages, 2614 KiB  
Hypothesis
Herpesvirus Infection of Endothelial Cells as a Systemic Pathological Axis in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
by Jean M. Nunes, Douglas B. Kell and Etheresia Pretorius
Viruses 2024, 16(4), 572; https://doi.org/10.3390/v16040572 - 8 Apr 2024
Cited by 2 | Viewed by 8983
Abstract
Understanding the pathophysiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is critical for advancing treatment options. This review explores the novel hypothesis that a herpesvirus infection of endothelial cells (ECs) may underlie ME/CFS symptomatology. We review evidence linking herpesviruses to persistent EC infection and [...] Read more.
Understanding the pathophysiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is critical for advancing treatment options. This review explores the novel hypothesis that a herpesvirus infection of endothelial cells (ECs) may underlie ME/CFS symptomatology. We review evidence linking herpesviruses to persistent EC infection and the implications for endothelial dysfunction, encompassing blood flow regulation, coagulation, and cognitive impairment—symptoms consistent with ME/CFS and Long COVID. This paper provides a synthesis of current research on herpesvirus latency and reactivation, detailing the impact on ECs and subsequent systemic complications, including latent modulation and long-term maladaptation. We suggest that the chronicity of ME/CFS symptoms and the multisystemic nature of the disease may be partly attributable to herpesvirus-induced endothelial maladaptation. Our conclusions underscore the necessity for further investigation into the prevalence and load of herpesvirus infection within the ECs of ME/CFS patients. This review offers conceptual advances by proposing an endothelial infection model as a systemic mechanism contributing to ME/CFS, steering future research toward potentially unexplored avenues in understanding and treating this complex syndrome. Full article
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