Dynamic clade transitions and the influence of vaccine rollout on the spatiotemporal circulation of SARS-CoV-2 variants in São Paulo, Brazil.

Since 2021, the emergence of variants of concern (VOC) has led Brazil to experience record numbers of in COVID-19 cases and deaths. The expanded spread of the SARS-CoV-2 combined with a low vaccination rate has contributed to the emergence of new mutations that may enhance viral fitness, leading to the persistence of the disease. Due to limitations in the real-time genomic monitoring of new variants in some Brazilian states, we aimed to investigate whether genomic surveillance, coupled with epidemiological data and SARS-CoV-2 variants spatiotemporal spread in a smaller region, can reflect the pandemic progression at a national level. Our findings revealed three SARS-CoV-2 variant replacements from 2021 to early 2022, corresponding to the introduction and increase in the frequency of Gamma, Delta, and Omicron variants, as indicated by peaks of the Effective Reproductive Number (Reff). These distinct clade replacements triggered two waves of COVID-19 cases, influenced by the increasing vaccine uptake over time. Our results indicated that the effectiveness of vaccination in preventing new cases during the Delta and Omicron circulations was six and eleven times higher, respectively, than during the period when Gamma was predominant, and it was highly efficient in reducing the number of deaths. Furthermore, we demonstrated that genomic monitoring at a local level can reflect the national trends in the spread and evolution of SARS-CoV-2.

Viral metagenomics unveils MW (Malawi) polyomavirus infection in Brazilian pediatric patients with acute respiratory disease.

Viral metagenomics has been extensively applied for the identification of emerging or poorly characterized viruses. In this study, we applied metagenomics for the identification of viral infections among pediatric patients with acute respiratory disease, but who tested negative for SARS-CoV-2. Twelve pools composed of eight nasopharyngeal specimens were submitted to viral metagenomics. Surprisingly, in two of the pools, we identified reads belonging to the poorly characterized Malawi polyomavirus (MWPyV). Then, the samples composing the positive pools were individually tested using quantitative polymerase chain reaction for identification of the MWPyV index cases. MWPyV-positive samples were also submitted to respiratory virus panel testing due to the metagenomic identification of different clinically important viruses. Of note, MWPyV-positive samples tested also positive for respiratory syncytial virus types A and B. In this study, we retrieved two complete MWPyV genome sequences from the index samples that were submitted to phylogenetic inference to investigate their viral origin. Our study represents the first molecular and genomic characterization of MWPyV obtained from pediatric patients in South America. The detection of MWPyV in acutely infected infants suggests that this virus might participate (coparticipate) in cases of respiratory symptoms. Nevertheless, future studies based on testing of a larger number of clinical samples and MWPyV complete genomes appear to be necessary to elucidate if this emerging polyomavirus might be clinically important.

Correction: Short Report: Early genomic detection of SARS-CoV-2 P.1 variant in Northeast Brazil.

[This corrects the article DOI: 10.1371/journal.pntd.0009591.].

Short Report: Early genomic detection of SARS-CoV-2 P.1 variant in Northeast Brazil.

Tracking the spread of SARS-CoV-2 variants of concern is crucial to inform public health efforts and control the ongoing pandemic. Here, we report genetic evidence for circulation of the P.1 variant in Northeast Brazil. We advocate for increased active surveillance to ensure adequate control of this variant throughout the country.

Early transmission of SARS-CoV-2 in South Africa: An epidemiological and phylogenetic report.

OBJECTIVES: The Network for Genomic Surveillance in South Africa (NGS-SA) was formed to investigate the introduction and understand the early transmission dynamics of the SARS-CoV-2 epidemic in South-Africa. DESIGN: This paper presents the first results from this group, which is a molecular epidemiological study of the first 21 SARS-CoV-2 whole genomes sampled in the first port of entry - KwaZulu-Natal (KZN) - during the first month of the epidemic. By combining this with calculations of the effective reproduction number (R), it aimed to shed light on the patterns of infections in South Africa. RESULTS: Two of the largest provinces - Gauteng and KZN - had a slow growth rate for the number of detected cases, while the epidemic spread faster in the Western Cape and Eastern Cape. The estimates of transmission potential suggested a decrease towards R = 1 since the first cases and deaths, but a subsequent estimated R average of 1.39 between 6-18 May 2020. It was also demonstrated that early transmission in KZN was associated with multiple international introductions and dominated by lineages B1 and B. Evidence for locally acquired infections in a hospital in Durban within the first month of the epidemic was also provided. CONCLUSION: The COVID-19 pandemic in South Africa was very heterogeneous in its spatial dimension, with many distinct introductions of SARS-CoV2 in KZN and evidence of nosocomial transmission, which inflated early mortality in KZN. The epidemic at the local level was still developing and NGS-SA aimed to clarify the dynamics in South Africa and devise the most effective measures as the outbreak evolved.

Potential chimeric peptides to block the SARS-CoV-2 spike receptor-binding domain.

Background: There are no known medicines or vaccines to control the COVID-19 pandemic caused by SARS-CoV-2 (nCoV). Antiviral peptides are superior to conventional drugs and may also be effective against COVID-19. Hence, we investigated the SARS-CoV-2 Spike receptor-binding domain (nCoV-RBD) that interacts with hACE2 for viral attachment and entry. Methods: Three strategies and bioinformatics approaches were employed to design potential nCoV-RBD - hACE2 interaction-blocking peptides that may restrict viral attachment and entry. Firstly, the key residues interacting with nCoV-RBD - hACE2 are identified and hACE2 sequence-based peptides are designed. Second, peptides from five antibacterial peptide databases that block nCoV-RBD are identified; finally, a chimeric peptide design approach is used to design peptides that can bind to key nCoV-RBD residues. The final peptides are selected based on their physiochemical properties, numbers and positions of key residues binding, binding energy, and antiviral properties. Results: We found that: (i) three amino acid stretches in hACE2 interact with nCoV-RBD; (ii) effective peptides must bind to three key positions of nCoV-RBD (Gly485/Phe486/Asn487, Gln493, and Gln498/Thr500/Asn501); (iii) Phe486, Gln493, and Asn501 are critical residues; (iv) AC20 and AC23 derived from hACE2 may block two key critical positions; (iv) DBP6 identified from databases can block the three sites of the nCoV-RBD and interacts with one critical position, Gln498; (v) seven chimeric peptides were considered promising, among which cnCoVP-3, cnCoVP-4, and cnCoVP-7 are the top three; and (vi) cnCoVP-4 meets all the criteria and is the best peptide. Conclusions: To conclude, using three different bioinformatics approaches, we identified 17 peptides that can potentially bind to the nCoV-RBD that interacts with hACE2. Binding these peptides to nCoV-RBD may potentially inhibit the virus to access hACE2 and thereby may prevent the infection. Out of 17, 10 peptides have promising potential and need further experimental validation.

Computational screening for potential drug candidates against the SARS-CoV-2 main protease.

Background: SARS-CoV-2 is the causal agent of the current coronavirus disease 2019 (COVID-19) pandemic. They are enveloped, positive-sense, single-stranded RNA viruses of the Coronaviridae family. Proteases of SARS-CoV-2 are necessary for viral replication, structural assembly, and pathogenicity. The approximately 33.8 kDa M pro protease of SARS-CoV-2 is a non-human homologue and is highly conserved among several coronaviruses, indicating that M pro could be a potential drug target for Coronaviruses. Methods: Herein, we performed computational ligand screening of four pharmacophores (OEW, remdesivir, hydroxychloroquine and N3) that are presumed to have positive effects against SARS-CoV-2 M pro protease (6LU7), and also screened 50,000 natural compounds from the ZINC Database dataset against this protease target. Results: We found 40 pharmacophore-like structures of natural compounds from diverse chemical classes that exhibited better affinity of docking as compared to the known ligands. The 11 best selected ligands, namely ZINC1845382, ZINC1875405, ZINC2092396, ZINC2104424, ZINC44018332, ZINC2101723, ZINC2094526, ZINC2094304, ZINC2104482, ZINC3984030, and ZINC1531664, are mainly classified as beta-carboline, alkaloids, and polyflavonoids, and all displayed interactions with dyad CYS145 and HIS41 from the protease pocket in a similar way as other known ligands. Conclusions: Our results suggest that these 11 molecules could be effective against SARS-CoV-2 protease and may be subsequently tested in vitro and in vivo to develop novel drugs against this virus.

Measuring Mosquito-borne Viral Suitability in Myanmar and Implications for Local Zika Virus Transmission.

INTRODUCTION: In South East Asia, mosquito-borne viruses (MBVs) have long been a cause of high disease burden and significant economic costs. While in some SEA countries the epidemiology of MBVs is spatio-temporally well characterised and understood, in others such as Myanmar our understanding is largely incomplete. MATERIALS AND METHODS: Here, we use a simple mathematical approach to estimate a climate-driven suitability index aiming to better characterise the intrinsic, spatio-temporal potential of MBVs in Myanmar. RESULTS: Results show that the timing and amplitude of the natural oscillations of our suitability index are highly informative for the temporal patterns of DENV case counts at the country level, and a mosquito-abundance measure at a city level. When projected at fine spatial scales, the suitability index suggests that the time period of highest MBV transmission potential is between June and October independently of geographical location. Higher potential is nonetheless found along the middle axis of the country and in particular in the southern corridor of international borders with Thailand. DISCUSSION: This research complements and expands our current understanding of MBV transmission potential in Myanmar, by identifying key spatial heterogeneities and temporal windows of importance for surveillance and control. We discuss our findings in the context of Zika virus given its recent worldwide emergence, public health impact, and current lack of information on its epidemiology and transmission potential in Myanmar. The proposed suitability index here demonstrated is applicable to other regions of the world for which surveillance data is missing, either due to lack of resources or absence of an MBV of interest.

CD4+ T-cell Count may not be a Useful Strategy to Monitor Antiretroviral Therapy Response in HTLV-1/HIV Co-infected Patients.

BACKGROUND: HTLV-1/HIV co-infection is known to elevate the CD4+ T-cell counts of treatment-naïve persons. We investigated whether HTLV-1/HIV co-infected patients continued to have elevated CD4+ T-cell counts after developing virologic failure on antiretroviral therapy (ART). METHODS: The data is taken from a drug resistance study located in the KwaZulu-Natal province of South Africa. All participants (N=383) presented for repeated CD4+ T-cell count and HIV viral load level testing between January 2006 and March 2014. We used a random-coefficient model to estimate the change in CD4+ T-cell count and HIV viral load level by HTLV-1/HIV co-infection status over time, adjusting for age, sex, and duration of virologic failure. RESULTS: HTLV-1/HIV co-infected participants (n=8) had higher CD4+ T-cell counts, with a positive difference of 117.2 cells/µL at the ART initiation date (p-value=0.001), 114.7 cells/µL (pvalue< 0.001) 12 months after this date, and 112.3 cells/µL (p-value=0.005) 24 months after this date, holding all else constant. In contrast, there was no difference in the HIV viral load level by HTLV-1/HIV co-infected status throughout the observation period. CONCLUSION: We show that HTLV-1/HIV co-infected participants continued to have elevated CD4+ T-cell counts after developing virologic failure on ART, despite no difference in their HIV viral load levels when compared with HIV mono-infected participants. Our results indicate that CD4+ T-cell count testing may not be a useful strategy to monitor ART response in the presence of HTLV-1/HIV co-infection.

Epidemiology of Chikungunya Virus in Bahia, Brazil, 2014-2015.

Chikungunya is an emerging arbovirus that is characterized into four lineages. One of these, the Asian genotype, has spread rapidly in the Americas after its introduction in the Saint Martin island in October 2013. Unexpectedly, a new lineage, the East-Central-South African genotype, was introduced from Angola in the end of May 2014 in Feira de Santana (FSA), the second largest city in Bahia state, Brazil, where over 5,500 cases have now been reported. Number weekly cases of clinically confirmed CHIKV in FSA were analysed alongside with urban district of residence of CHIKV cases reported between June 2014 and October collected from the municipality's surveillance network. The number of cases per week from June 2014 until September 2015 reveals two distinct transmission waves. The first wave ignited in June and transmission ceased by December 2014. However, a second transmission wave started in January and peaked in May 2015, 8 months after the first wave peak, and this time in phase with Dengue virus and Zika virus transmission, which ceased when minimum temperature dropped to approximately 15°C. We find that shorter travelling times from the district where the outbreak first emerged to other urban districts of FSA were strongly associated with incidence in each district in 2014 (R(2)).