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Volume 4, Emitir 2 (2020)

Artigo de Pesquisa

Anti-Retroviral Therapy and Serum Protein Levels in HIV-1 Seropositive Patients: A Five-Year Retrospective Study

Akor Egbunu Shedrack, Musa Haruna, Eneojo-Abah Eleojo Gloria, Yisa Benjamin Nma, Emmanuel Friday Titus, Dickson Achimugu Musa, Joel Ikojo Oguche, Serah Shaibu, Salami Tijani, David Bukbuk and Samuel Ene j Abah

Background: Serum proteins designated as liver function biomarkers are used to evaluate patients for hepatic dysfunction. Hepatic effect of Anti-Retroviral Therapy (ART) needs further studies in HIV mono-infected patients. In this study, clinically defined patient datasets were analysed for protein levels in HIV-1 mono-infected seropositive patients with and without ART.

Materials and methods: Data were collected for the study groups, consisting of the control group and HIV-1 mono-infected seropositive patients with and without ART and were analysed statistically for differences among the groups. All subjects in the patient groups attended University of Maiduguri Teaching Hospital, Nigeria for a period of 5 years.

Result: The protein levels on initiation of ART were significantly higher than baseline levels (prior to ART). However, continuous use of ART for 5-year period did not induce any further significant change in protein levels. Receiver Operating Characteristic (ROC) curves shows that both Albumin (ALB) and Total protein (TP) levels discriminated among the study groups. The baseline levels of ALB in seropositive patients are significantly lower to levels on initiation of ART.

Conclusion: Continuous ART did not cause any further significant change in levels of liver function proteins than was observed on ART initiation. Hence, liver damage on continuous ART is not implied. Both ALB and TP levels could be important in HIV management of patients. Initiation of ART appears to elevate the low ALB level via a yet unknown mechanism and indicates possible role of ALB in ART mechanism of action.

Análise

Seasonality OF Respiratory Viruses Including SARS-CoV-2

N. Chandra Wickramasinghe*, Edward J. Steele, Ananda Nimalasuriya, Reginald M. Gorczynski, Gensuke Tokoro, Robert Temple and Milton Wainwright

We propose that a reservoir of respiratory viruses in clumps of micro-sized dust exists in tropospheric clouds from which virions can be seasonally released into the lower atmosphere and thence to ground level. Respiratory Syncytial Virus (RSV), Seasonal Influenza and Human Para Influenza Virus (HPIV) are all diseases that fall in this category, including SARS-CoV-2. The seasonal incidence of disease at ground level would appear to be patchy over distance scales that are largely dictated by viral-laden dust cloud size modulated by scales of atmospheric turbulence. This could produce clustering of cases in space and time that has given rise to ‘contagion’ concepts of community spread and of superspreaders.

Artigo de Pesquisa

Interaction Energies of the Human ACE2 Molecular Recognition by SARS-CoV-2

Joao Batista Junior*

The Coronaviridae family of viruses includes hundreds of viruses common in many different animal species and humans. Seven coronaviruses (CoVs) are known to cause disease in humans. Four of them show low pathogenicity and are endemic in humans and the other three CoV are particularly dangerous and highly pathogenic viruses, which underwent genetic changes rendering them able to jump the species barriers from animal host to humans and also to spread efficiently among humans. SARS-CoV-2 is the seventh coronavirus known to infect humans. The S protein mediates attachment and viral and host cell membrane fusion. The receptor-binding domains (RBDs) are regions in S protein responsible for receptor recognition. Human angiotensin-converting enzyme 2 (ACE2) is recognized by HCoV-NL63, SARS-CoV and SARS-CoV-2 as their functional receptor.

Interaction energy analysis were performed to unveil how precisely SARS-CoV-2 interacts with ACE2 by identifying which amino acid residues are responsible for the interactions across S protein-ACE2 interfaces and how they contribute to the strength, stability and specificity of S protein interactions.

Interaction energies acting on molecular recognition of ACE2 by HCoV-NL63, SARS-CoV and SARS-CoV-2 conduced to a naturally evolved RBD with different combinations of amino acids, providing SARS-CoV-2 binding interface more interacting residue pairs, more hydrogen bonds, increased number of residues engaged in hydrogen bonding, allowing for better distribution of hydrogen bond per residue in interface than SARS-CoV or HCoV-NL63, includes salt bridge, and adds new van der Waals contacts into the network.

Residues across the SARS-CoV and SARS-CoV -2 homologous sequences have been chosen to be remarkably evolutionary conserved in the regions mediating binding of these viruses because of their dominant hydrogen bonding contribution to binding stability to ACE2. SARS-CoV-2 achieves higher binding affinity than SARS-CoV and HCoV-NL63 to human ACE2 molecular recognition primarily by combining its richer interaction network and higher binding stability.

This study presents a comprehensive and quantitative analysis of interaction energies of the human ACE2 molecular recognition by CoVs that may contribute to further understand the higher infectivity and transmissibility of SARS-CoV-2 compared to SARS-CoV and HCoV-NL63, furthermore, this could help explain why SARS-CoV-2 has an enhanced ability for pathogenicity.

Artigo de Pesquisa

Implications of Haplotype Switching for the Origin and Global Spread of COVID-19

Edward J. Steele*, Reginald M. Gorczynski, Herbert Rebhan, Patrick Carnegie, Robert Temple, Gensuke Tokoro, Alexander Kondakov, Stephen G. Coulson, Dayal T. Wickramasinghe and N. Chandra Wickramasinghe*

When analysed in patients at epicentres of outbreaks over the first three months of the 2020 pandemic, the virus responsible for COVID-19 cannot be classed as a rapidly mutating virus. It employs a haplotype-switching strategy most likely driven by APOBEC and ADAR cytosine and adenosine deamination events (C>U, A>I) at key selected sites in the ~ 30,000 nt positive sense single-stranded RNA genome (Steele and Lindley 2020). Quite early on (China, through Jan 2020) the main haplotype was L with a minor proportion of the S haplotype. By the time of the explosive outbreaks in New York City (mid-to late-March 2020) the haplotype variants expanded to at least 13. The COVID-19 genomes analysed at the main sites of exponential increases in cases and deaths over a 2 week time period (explosive epicentres) such as Wuhan and New York City showed limited mutation per se of the main haplotypes engaged in disease. When mutation was detected it was usually conservative in terms of significant alterations to protein structure. The coronavirus haplotypes whether in Wuhan, West Coast USA, Spain or New York differ by no more than 2-9 coordinated nucleotide changes and all genomes are thus ≥ 99.98% identical to each other. Further, we show that the most similar SARS-like CoV animal virus sequences (bats, pangolins) could not have caused the assumed zoonotic event setting off this explosive pandemic in Wuhan and regions: zoonotic causation via a Chinese wild bat SL-CoV reservoir jumping to humans by an intermediate amplifier (e.g. pangolins) is clearly not possible on the basis of the available data. We also discuss the evidence for airborne transmission of COVID-19 as the main infection route and highlight outbreaks on certain ships at sea consistent with their hypothesised cosmic origins. We conclude that the virus originated as a pure genetic strain in a life-bearing carbonaceous meteorite which was first deposited in the tropospheric jet stream over Wuhan. Over the next month or so this viral-laden dust cloud not only descended through the troposphere to target Wuhan and its environs, but was also transported in a Westerly direction through the mid-latitude northern jet stream causing explosive in-fall events sequentially over Iran, Italy, Spain and then New York City in the early months of the pandemic to the end of March 2020.

Comunicação curta

Mid-Ocean Outbreaks of COVID-19 with Tell-Tale Signs of Aerial Incidence

George A. Howard, N.Chandra Wickramasinghe*, Herbert Rebhan, Edward J. Steele, Reginald M. Gorczynski, Robert Temple, Gensuke Tokoro, Brig Klyce, Predrag Slijepcevic, Max K. Wallis and Stephen J. Coulson

Outbreaks of COVID-19 in passengers and crew in ships at sea continue to pose a problem for conventional epidemiology. In one instance the crew of an Argentinian fishing trawler, who were quarantined and tested negative before sailing, contracted the disease after 35 days at sea. In another instance a livestock ship had crew that was isolated and confined becoming sick with presumed COVID-19 whilst sailing in mid-ocean.

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