A5042169672- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- SARS-CoV-2 and COVID-19 Research
- Biochemical and Molecular Research
- COVID-19 epidemiological studies
- COVID-19 Clinical Research Studies
- HIV/AIDS Research and Interventions
- SARS-CoV-2 detection and testing
- Mosquito-borne diseases and control
- Pneumocystis jirovecii pneumonia detection and treatment
- Immune responses and vaccinations
- Vaccine Coverage and Hesitancy
- vaccines and immunoinformatics approaches
- Animal Virus Infections Studies
- Long-Term Effects of COVID-19
- Viral Infections and Outbreaks Research
- Evolution and Genetic Dynamics
- Plant Virus Research Studies
- Malaria Research and Control
- Healthcare Systems and Reforms
- COVID-19 diagnosis using AI
- Aquaculture Nutrition and Growth
- Epigenetics and DNA Methylation
- Cytomegalovirus and herpesvirus research
- Aquaculture disease management and microbiota
University of Ghana
2020-2025
The Francis Crick Institute
2020-2025
Noguchi Memorial Institute for Medical Research
2020-2024
Cambridge Consultants (United Kingdom)
2023
Royal Society of Chemistry
2023
Institute for Systems Biology
2023
National University of Singapore
2023
University of Manchester
2023
Utrecht University
2023
National Institute of Plant Genome Research
2023
ABSTRACT Integrase (IN) strand transfer inhibitors (INSTIs) have been developed to inhibit the ability of HIV-1 integrase irreversibly link reverse-transcribed viral DNA host genome. INSTIs proven their high efficiency in inhibiting replication vitro and patients. However, first-generation only a modest genetic barrier resistance, allowing virus escape these powerful drugs through several resistance pathways. Second-generation INSTIs, such as dolutegravir (DTG, S/GSK1349572), reported higher...
Abstract Background Clinical studies have shown that integrase strand transfer inhibitors can be used to treat HIV-1 infection. Although the first-generation are susceptible emergence of resistance mutations impair their efficacy in therapy, such has not been identified date drug-naïve patients who treated with second-generation inhibitor dolutegravir. During previous vitro selection study, we a R263K mutation as most common substitution arise presence dolutegravir H51Y arising secondary...
Early career researchers (ECRs) are important stakeholders leading efforts to catalyze systemic change in research culture and practice. Here, we summarize the outputs from a virtual unconventional conference (unconference), which brought together 54 invited experts 20 countries with extensive experience ECR initiatives designed improve practice of science. Together, drafted 2 sets recommendations for (1) ECRs directly involved or activities practice; (2) who wish support these efforts....
ABSTRACT Recently, several phase 3 clinical trials (ECHO and THRIVE) showed that E138K M184I were the most frequent mutations to emerge in patients who failed therapy with rilpivirine (RPV) together two nucleos(t)ide reverse transcriptase inhibitors, emtricitabine (FTC) tenofovir (TDF). To investigate basis for copresence of M184I, we generated recombinant mutated wild-type (WT) (RT) enzymes HIV-1 NL4-3 infectious clones. Drug susceptibilities determined cord blood mononuclear cells (CBMCs)....
First-generation integrase strand-transfer inhibitors (INSTIs), such as raltegravir (RAL) and elvitegravir (EVG), have been clinically proven to be effective antiretrovirals for the treatment of HIV-positive patients. However, their relatively low genetic barrier resistance makes them susceptible emergence drug mutations. In contrast, dolutegravir (DTG) is a newer INSTI that appears high in vivo. mutation R263K followed by polymorphic substitution M50I has observed cell culture. The...
Dolutegravir (DTG) is the latest antiretroviral (ARV) approved for treatment of human immunodeficiency virus (HIV) infection. The G118R substitution, previously identified with MK-2048 and raltegravir, may represent initial substitution in a dolutegravir resistance pathway. We have found that subtype C integrase proteins low enzymatic cost associated mostly at strand transfer step integration, compared to either B or recombinant CRF02_AG proteins. Subtype circulating form AG (CRF02_AG)...
Abstract The COVID-19 pandemic is one of the fastest evolving pandemics in recent history. As such, SARS-CoV-2 viral evolution needs to be continuously tracked. This study sequenced 1123 genomes from patient isolates (121 arriving travellers and 1002 communities) track molecular spatio-temporal dynamics variants Ghana. data show that initial local transmission was dominated by B.1.1 lineage, but second wave overwhelmingly driven Alpha variant. Subsequently, an unheralded variant under...
Abstract Recombination is an evolutionary process by which many pathogens generate diversity and acquire novel functions. Although a common occurrence during coronavirus replication, detection of recombination only feasible when genetically distinct viruses contemporaneously infect the same host. Here, we identify instance SARS-CoV-2 superinfection, whereby individual was infected with two viral variants: Alpha (B.1.1.7) Epsilon (B.1.429). This superinfection first noted genome sequence...
Drug resistance mutations (DRMs) have been reported for all currently approved anti-HIV drugs, including the latest integrase strand transfer inhibitors (INSTIs). We previously used new INSTI dolutegravir (DTG) to select a G118R substitution in tissue culture and also showed that secondary substitutions emerged at positions H51Y E138K. Now, we characterized impact of substitution, alone or combination with either E138K, on 3' processing activity. The results show primarily impacted step...
Protein arginine methyltransferase 6 (PRMT6) is a nuclear enzyme that methylates residues on histones and transcription factors. In addition, PRMT6 inhibits HIV-1 replication in cell culture by directly methylating interfering with the functions of several proteins, i.e. Tat, Rev nucleocapsid (NC). also displays automethylation capacity but role this post-translational modification its antiretroviral activity remains unknown.Here we report identification liquid chromatography-mass...
Objective: Among 1222 antiretroviral-naive patients who received dolutegravir (DTG) as part of first-line therapy, none has developed resistance against this compound after 48–96 weeks follow-up. Moreover, only four occurrences virological failure with mutations have been documented in previously drug-experienced DTG a first time integrase inhibitor component second-line regimen. The R263K mutation was observed two these individuals suboptimal background regimens. We selected at position...
The SARS-CoV-2 genome occupies a unique place in infection biology - it is the most highly sequenced on earth (making up over 20% of public sequencing datasets) with fine scale information sampling date and geography, has been subject to unprecedented intense analysis. As result, these phylogenetic data are an incredibly valuable resource for science health. However, vast majority was by tiling amplicons across full genome, amplicon schemes that changed pandemic as mutations viral interacted...
BackgroundThe results of several clinical trials suggest that the integrase inhibitor dolutegravir may be less prone than other drugs to emergence HIV drug resistance mutations in treatment-naive patients. We have shown R263K mutation commonly emerged during tissue culture selection studies with and conferred low levels this while simultaneously diminishing both replication capacity enzymatic activity. E138K has been identified as a secondary for also observed clinic inhibitors raltegravir...
Malaria remains a significant global health challenge, with Plasmodium falciparum responsible for the majority of severe cases and fatalities. Targeting parasites invasion mechanisms offers promising therapeutic strategy. In this study, we leveraged novel agentic foundational model, Moremi Bio Agent, to design monoclonal antibodies targeting AMA1-RON2 complex, critical component in parasite's human red blood cells. Using advanced structural modeling, generated 999 antibodies, which were...
Dolutegravir has been recently approved for treatment-naive and -experienced HIV-infected subjects, including integrase inhibitor (INI)-experienced patients. is a second-generation INI that can overcome many prior raltegravir elvitegravir failures. Here, we report the evolution of resistance to dolutegravir in highly treatment-experienced patient harbouring major N155H mutation consequent treatment failure. Genotypic phenotypic analyses were done on longitudinal samples determine viral INIs....