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KHAN, MOHAMMAD ASİF

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MOHAMMAD ASİF
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KHAN
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    PublicationOpen Access
    Avian Influenza H7N9 Virus Adaptation to Human Hosts
    (2021-05-01T00:00:00Z) Tan, Swan; Sjaugi, Muhammad Farhan; Fong, Siew Chinn; Chong, Li Chuin; Abd Raman, Hadia Syahirah; Nik Mohamed, Nik Elena; August, Joseph Thomas; Khan, Asif M.; KHAN, MOHAMMAD ASİF
    Avian influenza virus A (H7N9), after circulating in avian hosts for decades, was identified as a human pathogen in 2013. Herein, amino acid substitutions possibly essential for human adaptation were identified by comparing the 4706 aligned overlapping nonamer position sequences (1-9, 2-10, etc.) of the reported 2014 and 2017 avian and human H7N9 datasets. The initial set of virus sequences (as of year 2014) exhibited a total of 109 avian-to-human (A2H) signature amino acid substitutions. Each represented the most prevalent substitution at a given avian virus nonamer position that was selectively adapted as the corresponding index (most prevalent sequence) of the human viruses. The majority of these avian substitutions were long-standing in the evolution of H7N9, and only 17 were first detected in 2013 as possibly essential for the initial human adaptation. Strikingly, continued evolution of the avian H7N9 virus has resulted in avian and human protein sequences that are almost identical. This rapid and continued adaptation of the avian H7N9 virus to the human host, with near identity of the avian and human viruses, is associated with increased human infection and a predicted greater risk of human-to-human transmission.
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    PublicationOpen Access
    Computational design and characterization of a multiepitope vaccine against carbapenemase-producing Klebsiella pneumoniae strains, derived from antigens identified through reverse vaccinology
    (2022-01-01T00:00:00Z) Cuscino, Nicola; Fatima, Ayesha; Di Pilato, Vincenzo; Bulati, Matteo; Alfano, Caterina; Monaca, Elisa; Di Mento, Giuseppina; Di Carlo, Daniele; Cardinale, Francesca; Monaco, Francesco; Rossolini, Gian Maria; KHAN, MOHAMMAD ASİF; Conaldi, Pier Giulio; Douradinha, Bruno; FATIMA, AYESHA; KHAN, MOHAMMAD ASİF
    Klebsiella pneumoniae is a Gram-negative pathogen of clinical relevance, which can provoke serious urinary and blood infections and pneumonia. This bacterium is a major public health threat due to its resistance to several antibiotic classes. Using a reverse vaccinology approach, 7 potential antigens were identified, of which 4 were present in most of the sequences of Italian carbapenem-resistant K. pneumoniae clinical isolates. Bioinformatics tools demonstrated the antigenic potential of these bacterial proteins and allowed for the identification of T and B cell epitopes. This led to a rational design and in silico characterization of a multiepitope vaccine against carbapenem-resistant K. pneumoniae strains. As adjuvant, the mycobacterial heparin-binding hemagglutinin adhesin (HBHA), which is a Toll-like receptor 4 (TLR-4) agonist, was included, to increase the immunogenicity of the construct. The multiepitope vaccine candidate was analyzed by bioinformatics tools to assess its antigenicity, solubility, allergenicity, toxicity, physical and chemical parameters, and secondary and tertiary structures. Molecular docking binding energies to TLR-2 and TLR-4, two important innate immunity receptors involved in the immune response against K. pneumoniae infections, and molecular dynamics simulations of such complexes supported active interactions. A codon optimized multiepitope sequence cloning strategy is proposed, for production of recombinant vaccine in classical bacterial vectors. Finally, a 3 dose-immunization simulation with the multiepitope construct induced both cellular and humoral immune responses. These results suggest that this multiepitope construct has potential as a vaccination strategy against carbapenem-resistant K. pneumoniae and deserves further validation.
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    PublicationOpen Access
    Dynamics of Influenza A (H5N1) virus protein sequence diversity
    (2020-05-01T00:00:00Z) Abd Raman, Hadia Syahirah; Tan, Swan; August, Joseph Thomas; Khan, Asif M.; KHAN, MOHAMMAD ASİF
    Background. InfluenzaA(H5N1) virus is a global concern with potential as a pandemic threat. High sequence variability of influenza A viruses is a major challenge for effective vaccine design. A continuing goal towards this is a greater understanding of influenza A (H5N1) proteome sequence diversity in the context of the immune system (antigenic diversity), the dynamics of mutation, and effective strategies to overcome the diversity for vaccine design.
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    PublicationOpen Access
    Editorial: Bioinformatics and the Translation of Data-Driven Discoveries
    (2022-05-01T00:00:00Z) KHAN, MOHAMMAD ASİF; Ranganathan, Shoba; Suravajhala, Prashanth; KHAN, MOHAMMAD ASİF