A systemic study on the vulnerability and fatality of prostate cancer patients towards COVID-19 through analysis of the TMPRSS2, CXCL10 and their co-expressed genes.

A pandemic of respiratory disease named coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is reported prostate cancer patients are susceptible to COVID-19 infection. To understand the possible causes of prostate cancer patients' increased vulnerability and mortality from COVID-19 infection, we focused on the two most important agents, transmembrane protease serine subtype 2 (TMPRSS2) and the C-X-C motif 10 (CXCL10). When SARS-CoV-2 binds to the host cell via S protein-angiotensin-converting enzyme-2 receptor interaction, TMPRSS2 contributes in the proteolytic cleavage of the S protein, allowing the viral and cellular membranes to fuse. CXCL10 is a cytokine found in elevated level in both COVID-19 and cancer-causing cytokine storm. We discovered that TMPRSS2 and CXCL10 are overexpressed in prostate cancer and COVID-19 using the UALCAN and GEPIA2 datasets. The functional importance of TMPRSS2 and CXCL10 in prostate cancer development was then determined by analyzing the frequency of genetic changes in their amino acid sequences using the cBioPortal online portal. Finally, we used the PANTHER database to examine the pathology of the targeted genes. We observed that TMPRSS2 and CXCL10, together with their often co-expressed genes, are important in the binding activity and immune responses in prostate cancer and COVID-19 infection, respectively. Finally, we found that TMPRSS2 and CXCL10 are two putative biomarkers responsible for the increased vulnerability and fatality of prostate cancer patients to COVID-19.

A next generation sequencing (NGS) analysis to reveal genomic and proteomic mutation landscapes of SARS-CoV-2 in South Asia.

Counts for SARS-CoV-2 associated infections and fatalities are on the rise globally even in regions which contained the spread momentarily. The pattern of infections has been found to be controlled by the distinctive selection pressures exerted by fluctuating environmental nature and hosts. A total of 410 whole-genome sequences submitted by the South Asian countries were retrieved from the GISAID database and analyzed to assess the impact and pattern of mutations in this region. Most common and frequent mutations in the South Asian countries are 241C > T, 3037C > T, 14408C > T, and 23403A > G and about 85% SNPs are localized in ORF1ab, spike protein, and nucleocapsid. Among the identified mutations, the proportion of missense type (54.17%) was highest, followed by the synonymous (41.66%) and the non-coding types (4.17%). While analyzing transmission source in terms of geolocation, the largest clustered group from the South Asian countries was based on the G-clade (D614G) (81.7%; 335/410 samples), tracing the inception and transmission of SARS-CoV-2 infections in the South Asian countries from European regions. Phylogenetic analysis also revealed that the South Asian strains are highly related to the South American and European strains. We found that G-clade mutations are more prevalent (96.19%) in the samples of Bangladesh which were also prevalent in the European isolates. Surprisingly, one missense mutation (1163A > T) in ORF1ab gene became dominant only in Bangladesh (78.8%), which led to debates regarding effects on the pathogenicity and transmissibility of the virus. Overall, the findings of this study highlight the frequently mutated SARS-CoV-2 variants among the COVID-19 patients in the South Asian countries which might ease containment of the disease in this region through investigating the virulence reducing factors as the identified mutations are strongly correlated with low infection and mortality rate.

Epitope-based universal vaccine for Human T-lymphotropic virus-1 (HTLV-1).

Human T-cell leukemia virus type 1 (HTLV-1) was the first oncogenic human retrovirus identified in humans which infects at least 10-15 million people worldwide. Large HTLV-1 endemic areas exist in Southern Japan, the Caribbean, Central and South America, the Middle East, Melanesia, and equatorial regions of Africa. HTLV-1 TAX viral protein is thought to play a critical role in HTLV-1 associated diseases. We have used numerous bio-informatics and immuno-informatics implements comprising sequence and construction tools for the construction of a 3D model and epitope prediction for HTLV-1 Tax viral protein. The conformational linear B-cell and T-cell epitopes for HTLV-1 TAX viral protein have been predicted for their possible collective use as vaccine candidates. Based on in silico investigation two B cell epitopes, KEADDNDHEPQISPGGLEPPSEKHFR and DGTPMISGPCPKDGQPS spanning from 324-349 and 252-268 respectively; and T cell epitopes, LLFGYPVYV, ITWPLLPHV and GLLPFHSTL ranging from 11-19, 163-171 and 233-241 were found most antigenic and immunogenic epitopes. Among different vaccine constructs generated by different combinations of these epitopes our predicted vaccine construct was found to be most antigenic with a score of 0.57. T cell epitopes interacted strongly with HLA-A*0201 suggesting a significant immune response evoked by these epitopes. Molecular docking study also showed a high binding affinity of the vaccine construct for TLR4. The study was carried out to predict antigenic determinants of the Tax protein along with the 3D protein modeling. The study revealed a potential multi epitope vaccine that can raise the desired immune response against HTLV-1 and be useful in developing effective vaccines against Human T-lymphotropic virus.

Screening of novel alkaloid inhibitors for vascular endothelial growth factor in cancer cells: an integrated computational approach.

Vascular endothelial growth factor (VEGF) is expressed at elevated levels by most cancer cells, which can stimulate vascular endothelial cell growth, survival, proliferation as well as trigger angiogenesis modulated by VEGF and VEGFR (a tyrosine kinase receptor) signaling. The angiogenic effects of the VEGF family are thought to be primarily mediated through the interaction of VEGF with VEGFR-2. Targeting this signaling molecule and its receptor is a novel approach for blocking angiogenesis. In recent years virtual high throughput screening has emerged as a widely accepted powerful technique in the identification of novel and diverse leads. The high resolution X-ray structure of VEGF has paved the way to introduce new small molecular inhibitors by structure-based virtual screening. In this study using different alkaloid molecules as potential novel inhibitors of VEGF, we proposed three alkaloid candidates for inhibiting VEGF and VEGFR mediated angiogenesis. As these three alkaloid compounds exhibited high scoring functions, which also highlights their high binding ability, it is evident that these alkaloids can be taken to further drug development pipelines for use as novel lead compounds to design new and effective drugs against cancer.

Evaluation of the susceptibility and fatality of lung cancer patients towards the COVID-19 infection: A systemic approach through analyzing the ACE2, CXCL10 and their co-expressed genes.

Coronavirus disease-2019 (COVID-19) is a recent world pandemic disease that is caused by a newly discovered strain of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS- CoV-2). Patients with comorbidities are most vulnerable to this disease. Therefore, cancer patients are reported to be more susceptible to COVID-19 infection, particularly lung cancer patients. To evaluate the probable reasons behind the excessive susceptibility and fatality of lung cancer patients to COVID-19 infection, we targeted the two most crucial agents, Angiotensin-converting enzyme 2 (ACE2) and C-X-C motif 10 (CXCL10). ACE2 is a receptor protein that plays a vital role in the entry of SARS-CoV-2 into the host cell and CXCL10 is a cytokine mainly responsible for the lung cell damage involving in a cytokine storm. By using the UALCAN and GEPIA2 databases, we observed that ACE2 and CXCL10 are mostly overexpressed in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). We then identified the functional significance of ACE2 and CXCL10 in lung cancer development by determining the genetic alteration frequency in their amino acid sequences using the cBioPortal web portal. Lastly, we did the pathological assessment of targeted genes using the PANTHER database. Here, we found that ACE2 and CXCL10 along with their commonly co-expressed genes are involved respectively in the binding activity and immune responses in case of lung cancer and COVID-19 infection. Finally, based on this systemic analysis, we concluded that ACE2 and CXCL10 are two possible biomarkers responsible for the higher susceptibility and fatality of lung cancer patients towards the COVID-19.