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Aim: Aim of this work was to design and identify some S-adenosyl-L-homocysteine (SAH) analogs as inhibitors of S-adenosyl-L-methionine-dependent methyltransferase (MTase) protein using computational approaches. Introduction: According to the current scenario the dengue has been a global burden. The people are being killed by dengue virus in an abundant number. Despite of lot of research being going on dengue worldwide, there is no single drug which can kill its virus. This creates an urge for new drug target identification and designing. MTase has been reported as an effective target against dengue virus as it catalyzes an essential step in methylation and capping of viral RNA for viral replication. Materials and Methods: The crystal structure of MTase in complex with SAH was used for designing new analogs of SAH. SAH analogs designed were analyzed on the basis of docking, ADMET, and toxicity analysis done using Discovery Studio 3.5. Results: Seventeen analogs found noncarcinogenic, nonmutagenic, as well as good ADMET properties and good drug-like profile. Conclusion: These SAH analogs, inhibitors of MTase may act as drugs against dengue virus. Further synthesis and biological testing against dengue virus is under observation. [ABSTRACT FROM AUTHOR]

The Zika virus disease is an Aedes mosquito-borne disease caused by the ZIKA virus. The unavailability of vaccines or proper chemotherapeutic treatment emphasizes the need for the development of preventive and therapeutic vaccines. T cell specific epitopes have been used as vaccine candidates to generate desired immune responses against a variety of viral pathogens. Herein, the immune-informatics approach was used for the screening of potential major histocompatibility complex class I restricted epitopes, which may be competent to generate a cell-mediated immune response in humans. A total of 63 epitopes were identified, which revealed a comprehensive binding affinity to the 42 different human leukocyte antigen class I supertypes: A01, A02, A08, A23, A24, A25, A26, A29, A30, A32, A66, A68, A69, A80, B07, B08, B14, B15, B27, B35, B39, B40, B42, B45, B46, B48, B51, B53, B54, B57, B58, B83, C12, C03, C04, C05, C06, C07, C08, C12, C14, and C15, and which had no homologs in humans. By combining the human leukocyte antigen binding specificity and population coverage, nine promiscuous epitopes located in Capsid 1 Protein (MVLAILAFL(P1)), Envelop Protein (RLKGVSYSL (P2) and RLITANPVI (P3)), NS2A (AILAALTPL (P4)), NS4B (LLVAHYMYL (P5) and LVAHYMYLI (P6)) and NS5 (SLINGVVRL (P7), ALNTFTNLV (P8) and YLSTQVRYL (P9)) were shortlisted. Most of these consensus epitopes revealed 100% conservancy in all Zika virus strains and were very less conserved against the human proteome. The combination of the selected epitopes accounted for an optimal coverage in the world wide population (> 99%) independent of ethnicity. Structural analysis of these selected epitopes by the PatchDock web server showed their preferential mode of presentation to the T cell receptor. All these results recommended the possibility of a combined epitope vaccine strategy and can therefore be further investigated for their immunological relevance and usefulness as vaccine candidates. [ABSTRACT FROM AUTHOR]

Cell-mediated immunity is important for the control of Ebola virus infection. We hypothesized that those HLA A0201 and HLA B40 restricted epitopes derived from Ebola virus proteins, would mount a good antigenic response. Here we employed an immunoinformatics approach to identify specific 9mer amino acid which may be capable of inducing a robust cell-mediated immune response in humans. We identified a set of 28 epitopes that had no homologs in humans. Specifically, the epitopes derived from NP, RdRp, GP and VP40 share population coverage of 93.40%, 84.15%, 74.94% and 77.12%, respectively. Based on the other HLA binding specificity and population coverage, seven novel promiscuous epitopes were identified. These 7 promiscuous epitopes from NP, RdRp and GP were found to have world-wide population coverage of more than 95% indicating their potential significance as useful candidates for vaccine design. Epitope conservancy analysis also suggested that most of the peptides are highly conserved (100%) in other virulent Ebola strain (Mayinga-76, Kikwit-95 and Makona-G3816- 2014) and can therefore be further investigated for their immunological relevance and usefulness as vaccine candidates. [ABSTRACT FROM AUTHOR]

Coronavirus disease-2019 (COVID-19) has become a global pandemic, necessitating the development of new medicines. In this investigation, we identified potential natural flavonoids and compared their inhibitory activity against spike glycoprotein, which is a target of SARS-CoV-2 and SARS-CoV. The target site for the interaction of new inhibitors for the treatment of SARS-CoV-2 has 82% sequence identity and the remaining 18% dissimilarities in RBD S1-subunit, S2-subunit, and 2.5% others. Molecular docking was employed to analyse the various binding processes used by each ligand in a library of 85 natural flavonoids that act as anti-viral medications and FDA authorised treatments for COVID-19. In the binding pocket of the target active site, remdesivir has less binding interaction than pectolinarin, according to the docking analysis. Pectolinarin is a natural flavonoid isolated from Cirsiumsetidensas that has anti-cancer, vasorelaxant, anti-inflammatory, hepatoprotective, anti-diabetic, anti-microbial, and anti-oxidant properties. The S-glycoprotein RBD region (330-583) is inhibited by kaempferol, rhoifolin, and herbacetin, but the S2 subunit (686-1270) is inhibited by pectolinarin, morin, and remdesivir. MD simulation analysis of S-glycoprotein of SARS-CoV-2 with pectolinarin complex at 100ns based on high dock-score. Finally, ADMET analysis was used to validate the proposed compounds with the highest binding energy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)