Biology subjects

Chowdhury, M. M. H.

Publications and source records attributed to Chowdhury, M. M. H..

4 recordsLinked to original sources

bioRxiv2025

Molecular Insights into Long COVID: Plasma Proteomics Reveals Oxidative Stress, Coagulation Cascade Activation, and Glycolytic Imbalance

Persistent symptoms following SARS-CoV-2 infection are the hallmark of post-COVID condition (PCC), also referred to as long COVID. However, our knowledge is limited on the underlying molecular mechanisms. In this study, we performed data-independent acquisition mass spectrometry plasma proteomics (DIA-MS) to identify molecular alterations associated with PCC. DIA-MS proteomic analysis revealed a few proteins linked to oxidative stress that had altered expression. Notably, PCC samples exhibited downregulation of the antioxidant protein peroxiredoxin 6 (PRDX6) and upregulation of oxidative stress-associated proteins particularly vanin-1 (VNN1) and paraoxonase-3 (PON3). Additionally, the PCC group showed significantly higher levels of six proteins (PCSK9, CST3, C1Q, CPB2, KNG1 GAPDH), which were linked to pathways involving glycolysis, complement and coagulation cascades, and inflammation. Oxidative stress analysis confirmed that PCC samples had significantly higher levels of DNA damage (8-OHdG) than the convalescent group, whereas antioxidant markers, such as reduced and oxidized glutathione (GSH and GSSG), were significantly lower in PCC samples than in uninfected controls. Our observations point towards ongoing oxidative and inflammatory processes in PCC and suggest potential targets for biomarker development and therapeutic intervention.

immunology↗

bioRxiv2023

SARS-CoV-2 spike antigen-specific B cell and antibody responses in pre-vaccination period COVID-19 convalescent males and females with or without post-covid condition

BackgroundFollowing SARS-CoV-2 infection a significant proportion of convalescent individuals develop the post-COVID condition (PCC) that is characterized by wide spectrum of symptoms encompassing various organs. Even though the underlying pathophysiology of PCC is not known, detection of viral transcripts and antigens in tissues other than lungs raise the possibility that PCC may be a consequence of aberrant immune response to the viral antigens. To test this hypothesis, we evaluated B cell and antibody responses to the SARS-CoV-2 antigens in PCC patients who experienced mild COVID-19 disease during the pre-vaccination period of COVID-19 pandemic. MethodsThe study subjects included unvaccinated male and female subjects who developed PCC or not (No-PCC) after clearing RT-PCR confirmed mild COVID-19 infection. SARS-CoV-2 D614G and omicron RBD specific B cell subsets in peripheral circulation were assessed by flow cytometry. IgG, IgG3 and IgA antibody titers toward RBD, spike and nucleocapsid antigens in the plasma were evaluated by ELISA. ResultsThe frequency of the B cells specific to D614G-RBD were comparable in convalescent groups with and without PCC in both males and females. Notably, in females with PCC, the anti-D614G RBD specific double negative (IgD-CD27-) B cells showed significant correlation with the number of symptoms at acute of infection. Anti-spike antibody responses were also higher at 3 months post-infection in females who developed PCC, but not in the male PCC group. On the other hand, the male PCC group also showed consistently high anti-RBD IgG responses compared to all other groups. ConclusionsThe antibody responses to the spike protein, but not the RBD-specific B cell responses diverge between convalescent males and females, and those who develop PCC or not. Our findings suggest that sex-related factors may also be involved in the development of PCC via modulating antibody responses to the SARS-CoV-2 antigens. Short SummaryPost-COVID Condition (PCC) is lingering illness that afflicts a significant proportion of COVID-19 patients from three months after clearing SARS-CoV-2 infection. Therapy for PCC is only palliative and the underlying disease mechanisms are unclear. The wide spectrum of PCC symptoms that can affect different organs and the detection of viral components in tissues distant from lungs raise the possibility that PCC may be associated with aberrant immune response due to presence of viral antigens. Therefore, we studied B cell and antibody responses to the spike and nucleoprotein antigens in PCC patients who cleared mild SARS-CoV-2 infection during the pre-vaccination COVID-19 pandemic period. We observed divergent patterns of immune reactivity to the spike protein in PCC males and females at different times post-infection, suggesting that the immune responses in PCC may also be influenced by sex-related factors.

immunology↗

bioRxiv2020

Plant derived bioactive compounds as potential inhibitors of ZIKA virus: an in silico investigation

The ZIKA virus has caused a heavy concern everywhere the globe because of its high infectivity and mortality rate. Still, theres no specific drug or preventive medication to treat ZIKA infection despite comprehensive analysis by the researchers. This study was designed to demonstrate the efficacy of some plant derived bioactive compounds against ZIKV by using both structure and ligand based virtual screening methods. A number of 35 plant metabolites were screened against ZIKA NS2B-NS3 protease (5LC0), Envelop protein (5JHM), Capsid protein (5YGH) and NS5 RNA-dependent RNA polymerase protein (5U04) employing molecular docking approach. Results showed that there have been four metabolites, i.e. Chicoric acid, Luteone, Reserpine and Rosmarinic acid provide highest binding affinity to targeted ZIKV proteins. Crucial binding sites and drug surface hotspots are unraveled for every targeted viral protein. The ADME study showed that neither of the candidate compounds had side effects that would reduce their drug-like properties. As compared, the toxicity pattern analysis has unmasked the non-toxic essence of top drug candidates. The RMSD values of ligand-macromolecule complexes were 2 [A] apart from Envelop protein- Chicoric Acid, although the RMSF values showed normal atomic fluctuations within the molecular dynamics analysis, with the exception of Envelop protein- Chicoric Acid. The expected majority of the target class the highest drug candidates is enzyme classes (e.g. protease, hydrolase, phosphatase). In addition, the drug similarity prediction revealed several structural analogs from drugbank such as Isoformononetin (DB04202), Deserpidine (DB01089) and Rescinnamine (DB01180) etc. and these analogs could even be an option for the treatment of ZIKV infections. The study can pave the way for the creation of effective ZIKV medications and preventive measures. We highly recommend further in vivo trials for the experimental validation of our findings.

bioinformatics↗

bioRxiv2020

BANCOVID, the first D614G variant mRNA-based vaccine candidate against SARS-CoV-2 elicits neutralizing antibody and balanced cellular immune response

Effective vaccine against SARS-CoV-2 is the utmost importance in the current world. More than 1 million deaths are accounted for relevant pandemic disease COVID-19. Recent data showed that D614G genotype of the virus is highly infectious and responsible for almost all infection for 2nd wave. Despite of multiple vaccine development initiatives, there are currently no report that has addressed this critical variant D614G as vaccine candidate. Here we report the development of an mRNA-LNP vaccine considering the D614G variant and characterization of the vaccine in preclinical trial. The surface plasmon resonance (SPR) data with spike protein as probe and competitive neutralization with RBD and S2 domain revealed that immunization generated specific antibody pools against the whole extracellular domain (RBD and S2) of the spike protein. The anti-sera and purified IgGs from immunized mice on day 7 and 14 neutralized SARS-CoV-2 pseudovirus in ACE2-expressing HEK293 cells in a dose dependent manner. Importantly, immunization protected mice lungs from pseudovirus entry and cytopathy. The immunologic responses have been implicated by a balanced and stable population of CD4+ cells with a Th1 bias. The IgG2a to IgG1 and (IgG2a+IgG2b) to (IgG1+IgG3) ratios were found 1{+/-}0.2 and 1.24{+/-}0.1, respectively. These values are comparatively higher than relevant values for other published SARS-CoV-2 vaccine in development,1, 2 and suggesting higher viral clearance capacity for our vaccine. The data suggested great promise for immediate translation of the technology to the clinic.

immunology↗