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  1. Article ; Online: Missense mutations in spike protein of SARS-CoV-2 delta variant contribute to the alteration in viral structure and interaction with hACE2 receptor.

    Mahmood, Tousif Bin / Hossan, Mohammad Imran / Mahmud, Shafi / Shimu, Mst Sharmin Sultana / Alam, Md Jahidul / Bhuyan, Md Mahfuzur Rahman / Emran, Talha Bin

    Immunity, inflammation and disease

    2022  Volume 10, Issue 9, Page(s) e683

    Abstract: Introduction: Many of the global pandemics threaten human existence over the decades among which coronavirus disease (COVID-19) is the newest exposure circulating worldwide. The RNA encoded severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ... ...

    Abstract Introduction: Many of the global pandemics threaten human existence over the decades among which coronavirus disease (COVID-19) is the newest exposure circulating worldwide. The RNA encoded severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is referred as the pivotal agent of this deadly disease that induces respiratory tract infection by interacting host ACE2 receptor with its spike glycoprotein. Rapidly evolving nature of this virus modified into new variants helps in perpetrating immune escape and protection against host defense mechanism. Consequently, a new isolate, delta variant originated from India is spreading perilously at a higher infection rate.
    Methods: In this study, we focused to understand the conformational and functional significance of the missense mutations found in the spike glycoprotein of SARS-CoV-2 delta variant performing different computational analysis.
    Results: From physiochemical analysis, we found that the acidic isoelectric point of the virus elevated to basic pH level due to the mutations. The targeted mutations were also found to change the interactive bonding pattern and conformational stability analyzed by the molecular dynamic's simulation. The molecular docking study also revealed that L452R and T478K mutations found in the RBD domain of delta variant spike protein contributed to alter interaction with the host ACE2 receptor.
    Conclusions: Overall, this study provided insightful evidence to understand the morphological and attributive impact of the mutations on SARS-CoV-2 delta variant.
    MeSH term(s) Angiotensin-Converting Enzyme 2/chemistry ; Angiotensin-Converting Enzyme 2/genetics ; Angiotensin-Converting Enzyme 2/metabolism ; COVID-19/genetics ; Humans ; Molecular Docking Simulation ; Mutation, Missense ; Peptidyl-Dipeptidase A/metabolism ; Protein Binding ; SARS-CoV-2/genetics ; Spike Glycoprotein, Coronavirus/genetics ; Viral Structures/metabolism
    Chemical Substances Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
    Language English
    Publishing date 2022-08-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 2740382-8
    ISSN 2050-4527 ; 2050-4527
    ISSN (online) 2050-4527
    ISSN 2050-4527
    DOI 10.1002/iid3.683
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: 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.

    Mahmood, Tousif Bin / Chowdhury, Afrin Sultana / Hossain, Mohammad Uzzal / Hasan, Mehedee / Mizan, Shagufta / Aakil, Md Mezbah-Ul-Islam / Hossan, Mohammad Imran

    Current research in microbial sciences

    2021  Volume 2, Page(s) 100022

    Abstract: 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. ... ...

    Abstract 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.
    Language English
    Publishing date 2021-02-09
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2666-5174
    ISSN (online) 2666-5174
    DOI 10.1016/j.crmicr.2021.100022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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

    Mahmood, Tousif Bin / Saha, Ayan / Hossan, Mohammad Imran / Mizan, Shagufta / Arman, S M Abu Sufian / Chowdhury, Afrin Sultana

    Current research in microbial sciences

    2021  Volume 2, Page(s) 100065

    Abstract: 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 ... ...

    Abstract 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 >
    Language English
    Publishing date 2021-08-24
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2666-5174
    ISSN (online) 2666-5174
    DOI 10.1016/j.crmicr.2021.100065
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Assessment of ACE2, CXCL10 and Their co-expressed Genes: An In-silico Approach to Evaluate the Susceptibility and Fatality of Lung Cancer Patients towards COVID-19 Infection

    Mahmood, Tousif Bin / Chowdhury, Afrin Sultana / Hasan, Mehedee / Aakil, Md. Mezbah-Ul-Islam / Hossan, Mohammad Imran

    bioRxiv

    Abstract: Background: COVID-19 is a recent pandemic that started to spread out worldwide from Wuhan, China. This disease is caused by a newly discovered strain of the coronavirus, namely SARS CoV-2. Lung cancer patients are reported to be more susceptible to COVID- ...

    Abstract Background: COVID-19 is a recent pandemic that started to spread out worldwide from Wuhan, China. This disease is caused by a newly discovered strain of the coronavirus, namely SARS CoV-2. Lung cancer patients are reported to be more susceptible to COVID-19 infection. To evaluate the probable reasons behind the excessive susceptibility and fatality of lung cancer patients to COVID-19 infection, we targeted two most crucial biomarkers of COVID-19, ACE2 and CXCL10. ACE2 plays a vital role in the SARS CoV-2 entry into the host cell while CXCL10 is a cytokine mainly responsible for the lung cell damage involving in a cytokine storm. Methods: Firstly, we used the TIMER, UALCAN and GEPIA2 databases to analyze the expression and correlation of ACE2 and CXCL10 in LUAD and LUSC. After that, using the cBioPortal database, we performed an analytical study to determine the genetic changes in ACE2 and CXCL10 protein sequences that are responsible for lung cancer development. Finally, we analyzed different functional approaches of ACE2, CXCL10 and their co-expressed genes associated with lung cancer and COVID-19 development by using the PANTHER database. Results: Initially, we observed that ACE2 and CXCL10 are mostly overexpressed in LUAD and LUSC. We also found the functional significance of ACE2 and CXCL10 in lung cancer development by determining the genetic alteration frequency in their amino acid sequences. Lastly, by doing the functional assessment of the targeted genes, we identified that ACE2 and CXCL10 along with their commonly co-expressed genes are respectively involved in the binding activity and immune responses in case of lung cancer and COVID-19 infection. Conclusions: Finally, on the basis of this systemic analysis, we came to the conclusion that ACE2 and CXCL10 are possible biomarkers responsible for the higher susceptibility and fatality of lung cancer patients towards the COVID-19.
    Keywords covid19
    Language English
    Publishing date 2020-05-27
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2020.05.27.119610
    Database COVID19

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  5. Article ; Online: Assessment of ACE2, CXCL10 and Their co-expressed Genes: An In-silico Approach to Evaluate the Susceptibility and Fatality of Lung Cancer Patients towards COVID-19 Infection

    Mahmood, Tousif Bin / Chowdhury, Afrin Sultana / Hasan, Mehedee / Aakil, Md. Mezbah-Ul-Islam / Hossan, Mohammad Imran

    bioRxiv

    Abstract: Background COVID-19 is a recent pandemic that started to spread out worldwide from Wuhan, China. This disease is caused by a newly discovered strain of the coronavirus, namely SARS CoV-2. Lung cancer patients are reported to be more susceptible to COVID- ... ...

    Abstract Background COVID-19 is a recent pandemic that started to spread out worldwide from Wuhan, China. This disease is caused by a newly discovered strain of the coronavirus, namely SARS CoV-2. Lung cancer patients are reported to be more susceptible to COVID-19 infection. To evaluate the probable reasons behind the excessive susceptibility and fatality of lung cancer patients to COVID-19 infection, we targeted two most crucial biomarkers of COVID-19, ACE2 and CXCL10. ACE2 plays a vital role in the SARS CoV-2 entry into the host cell while CXCL10 is a cytokine mainly responsible for the lung cell damage involving in a cytokine storm. Methods Firstly, we used the TIMER, UALCAN and GEPIA2 databases to analyze the expression and correlation of ACE2 and CXCL10 in LUAD and LUSC. After that, using the cBioPortal database, we performed an analytical study to determine the genetic changes in ACE2 and CXCL10 protein sequences that are responsible for lung cancer development. Finally, we analyzed different functional approaches of ACE2, CXCL10 and their co-expressed genes associated with lung cancer and COVID-19 development by using the PANTHER database. Results Initially, we observed that ACE2 and CXCL10 are mostly overexpressed in LUAD and LUSC. We also found the functional significance of ACE2 and CXCL10 in lung cancer development by determining the genetic alteration frequency in their amino acid sequences. Lastly, by doing the functional assessment of the targeted genes, we identified that ACE2 and CXCL10 along with their commonly co-expressed genes are respectively involved in the binding activity and immune responses in case of lung cancer and COVID-19 infection. Conclusions Finally, on the basis of this systemic analysis, we came to the conclusion that ACE2 and CXCL10 are possible biomarkers responsible for the higher susceptibility and fatality of lung cancer patients towards the COVID-19.
    Keywords covid19
    Publisher BioRxiv; WHO
    Document type Article ; Online
    DOI 10.1101/2020.05.27.119610
    Database COVID19

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  6. Article ; Online: Repurposing Remdesivir for COVID-19: Computational Drug Design Targeting SARS-CoV-2 RNA Polymerase and Main Protease using Molecular Dynamics Approach

    Shikder, Mita / Ahmed, Kazi Ahsan / Moin, Abu Tayab / Patil, Rajesh B. / Hasib, Tasnin Al / Hossan, Mohammad Imran / Mahasin, Deera / Sakib, Mohammad Najmul / Ahmed, Iqrar / Patel, Harun / Chowdhury, Afrin Sultana

    bioRxiv

    Abstract: The coronavirus disease of 2019 (COVID-19) is a highly contagious respiratory illness that has become a global health crisis with new variants, an unprecedented number of infections, and deaths and demands urgent manufacturing of potent therapeutics. ... ...

    Abstract The coronavirus disease of 2019 (COVID-19) is a highly contagious respiratory illness that has become a global health crisis with new variants, an unprecedented number of infections, and deaths and demands urgent manufacturing of potent therapeutics. Despite the success of vaccination campaigns around the globe, there is no particular therapeutics approved to date for efficiently treating infected individuals. Repositioning or repurposing previously effective antivirals against RNA viruses to treat COVID-19 patients is a feasible option. Remdesivir is a broad-spectrum antiviral drug that the Food and Drug Administration (FDA) licenses for treating COVID-19 patients who are critically ill patients. Remdesivir9s low efficacy, which has been shown in some clinical trials, possible adverse effects, and dose-related toxicities are issues with its use in clinical use. Our study aimed to design potent derivatives of remdesivir through the functional group modification of the parent drug targeting RNA-dependent RNA polymerase (RdRp) and main protease (MPro) of SARS-CoV-2. The efficacy and stability of the proposed derivatives were assessed by molecular docking and extended molecular dynamics simulation analyses. Furthermore, the pharmacokinetic activity was measured to ensure the safety and drug potential of the designed derivatives. The derivatives were non-carcinogenic, chemically reactive, highly interactive, and stable with the target proteins. D-CF3 is one of the designed derivatives that finally showed stronger interaction than the parent drug, according to the docking and dynamics simulation analyses, with both target proteins. However, in vitro and in vivo investigations are guaranteed to validate the findings in the future. Keywords: SARS-CoV-2; RNA-dependent RNA polymerase (RdRp); Main protease (MPro); Remdesivir; Modified derivatives; Molecular docking; Molecular dynamics simulation.
    Keywords covid19
    Language English
    Publishing date 2023-06-16
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2023.06.15.545129
    Database COVID19

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