Molecular Docking used as an advanced tool to determine novel compounds on emerging infectious diseases: A systematic review

Abstract Emerging infectious diseases (EIDs) are among the major problems impacted on global economics and healthful living. EIDs have long been perceive as a predominant conclusion of host-pathogen adaptation. Hence, in this analysis, influence by the appearance of major factors that impact emerging infectious diseases and explicate some extensive EIDs like HIV/AIDs, H1N1 and Coronavirus. A wealth of new trends, especially in applied science is fetching progressively for the fast molecular recognizable proof of microorganisms and the more precise checking of infectious disease movement. Atomic docking is one of the prominent computational tools, involving in construction put together medication disclosure with respect to EIDs to evaluate the limiting affinities between little particles and macromolecule that can further, used as a target of HIV/AIDs, H1N1, and coronavirus. Molecular approach of influenza neuraminidase, HIV-1 protease and Spike protein of corona virus result shows Zanamivir, Nelfinavir, Saquinavir, Erythromycin and Spiramycin are favourable interaction against the selected target proteins. These novel drug compounds approved in vivo studies with reaffirm results, it is clear that the computational methods (mainly molecular docking) are found to be an effective technique for drug discovery.

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Predicting binding modes and affinities for non-nucleoside inhibitors to HIV-1 reverse transcriptase using molecular docking

Science and Technology Development Journal - Natural Sciences ◽

10.32508/stdjns.v2i1.674 ◽

2019 ◽

Vol 2 (1) ◽

pp. 53-58

Author(s):

Nguyen Truong Tien ◽

Bui Tho Thanh

Keyword(s):

Molecular Docking ◽

Reverse Transcriptase ◽

Binding Pocket ◽

The Body ◽

Binding Modes ◽

Weakly Bound ◽

Hiv Drugs ◽

Anti Hiv ◽

Hiv 1 ◽

Hiv Aids

The HIV/AIDS epidemic has become one of the most dangerous causes leading to millions of deaths around the world a year. To date, there have not had effective anti-HIV drugs in the treatment of HIV/AIDS because of emerging drug-resistant HIV mutants. In this work, potential non-nucleoside reverse transcriptase inhibitors (NNRTIs) were studied by means of molecular docking. The Diversity “drug-like” database from the National Cancer Institute, is composed of 1.420 compounds, was performed docking into the NNRTI binding pocket of HIV-1 reverse transcriptase crystal structure (1fk9) by using Autodock version 4.2.6. Pharmacokinetic properties (absorption, distribution, metabolism and excretion (ADME)) and toxicity of potential inhibitors within the body were predicted by the PreADMET version 2.0. The obtained results point out that the compound, coded 2518, was discovered as a potential inhibitor that has good human intestinal absorption, weakly bound to plasma proteins as well as is negative to mutagenicity and carcinogenicity. This rational inhibitor would be further studied in order to contribute informations finding new anti-HIV drugs.

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Multivalent DNA Vaccines as A Strategy to Combat Multiple Concurrent Epidemics: Mosquito-Borne and Hemorrhagic Fever Viruses

Viruses ◽

10.3390/v13030382 ◽

2021 ◽

Vol 13 (3) ◽

pp. 382

Author(s):

Jingjing Jiang ◽

Stephanie J. Ramos ◽

Preeti Bangalore ◽

Dustin Elwood ◽

Kathleen A. Cashman ◽

...

Keyword(s):

Infectious Diseases ◽

Vaccine Development ◽

Dna Vaccines ◽

Specific Binding ◽

Emerging Infectious Diseases ◽

Hemorrhagic Fever ◽

Immune Memory ◽

Global Public Health ◽

Vaccine Platform

The emergence of multiple concurrent infectious diseases localized in the world creates a complex burden on global public health systems. Outbreaks of Ebola, Lassa, and Marburg viruses in overlapping regions of central and West Africa and the co-circulation of Zika, Dengue, and Chikungunya viruses in areas with A. aegypti mosquitos highlight the need for a rapidly deployable, safe, and versatile vaccine platform readily available to respond. The DNA vaccine platform stands out as such an application. Here, we present proof-of-concept studies from mice, guinea pigs, and nonhuman primates for two multivalent DNA vaccines delivered using in vivo electroporation (EP) targeting mosquito-borne (MMBV) and hemorrhagic fever (MHFV) viruses. Immunization with MMBV or MHFV vaccines via intradermal EP delivery generated robust cellular and humoral immune responses against all target viral antigens in all species. MMBV vaccine generated antigen-specific binding antibodies and IFNγ-secreting lymphocytes detected in NHPs up to six months post final immunization, suggesting induction of long-term immune memory. Serum from MHFV vaccinated NHPs demonstrated neutralizing activity in Ebola, Lassa, and Marburg pseudovirus assays indicating the potential to offer protection. Together, these data strongly support and demonstrate the versatility of DNA vaccines as a multivalent vaccine development platform for emerging infectious diseases.

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Plant Based Diet- A Therapeutic Riposte to Emerging Zoonotic Infections

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2020/45694.13977 ◽

2020 ◽

Author(s):

Praveen Jodalli ◽

Amitha Basheer ◽

Aradhana Nagarsekar ◽

Ridhima Gaunkar ◽

KM Ramya

Keyword(s):

Infectious Diseases ◽

Food System ◽

Emerging Infectious Diseases ◽

Swine Influenza ◽

World Health Organisation ◽

World Health ◽

Healthy Plant ◽

Economic Damage ◽

Zoonotic Infections ◽

Major Factors

Emerging zoonotic infectious diseases like swine influenza, avian influenza and Ebola have caused massive human suffering, social upheaval and economic damage across countries and continents. There is increasing evidence that humanity’s overexploitation of nature is one of the major factors responsible for the spread. Recently, mankind is traversing a hard-pandemic time due to COVID-19 outbreak which appears to be a brutal killer. When humans infringe wild adobes for food production, it generates opportunities for infectious pathogens to leap to livestock and humans. It is the time to begin brooding about more radical measures to handle the root of this crisis. A resilient food system that puts less stress on the environment would reduce the outbreak of Emerging Infectious Diseases (EID) by reducing contact between humans and wild animals thereby restoring biodiversity. World Health Organisation (WHO) advises avoidance/judicious use of animal meat consumption during or after every outbreak. It is clearly evident that a balanced, healthy plant-based diet can help to control pandemics/epidemics not only by preventing the transmission but also by strengthening the immune system of individuals to combat the infection. This paper throws light on how the human diet is directly or indirectly linked to the emergence, spread and prognosis of various infectious diseases.

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Implications of human activities for (re)emerging infectious diseases, including COVID-19

Journal of PHYSIOLOGICAL ANTHROPOLOGY ◽

10.1186/s40101-020-00239-5 ◽

2020 ◽

Vol 39 (1) ◽

Author(s):

Nundu Sabiti Sabin ◽

Akintije Simba Calliope ◽

Shirley Victoria Simpson ◽

Hiroaki Arima ◽

Hiromu Ito ◽

...

Keyword(s):

Infectious Diseases ◽

Human Activities ◽

Emerging Infectious Diseases ◽

Good Health ◽

Early Warning Systems ◽

First Century ◽

Health Maintenance ◽

Control And Prevention ◽

Major Factors ◽

Disease Epidemics

Abstract Since 1980, the world has been threatened by different waves of emerging disease epidemics. In the twenty-first century, these diseases have become an increasing global concern because of their health and economic impacts in both developed and resource-constrained countries. It is difficult to stop the occurrence of new pathogens in the future due to the interconnection among humans, animals, and the environment. However, it is possible to face a new disease or to reduce the risk of its spread by implementing better early warning systems and effective disease control and prevention, e.g., effective global surveillance, development of technology for better diagnostics, effective treatments, and vaccines, the global political will to respond to any threats and multidisciplinary collaboration involving all sectors in charge of good health maintenance. In this review, we generally describe some factors related to human activities and show how they can play a role in the transmission and spread of infectious diseases by using some diseases as examples. Additionally, we describe and discuss major factors that are facilitating the spread of the new pandemic known as COVID-19 worldwide.

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Molecular docking of (5E)-3-(2-aminoethyl)-5-(2-thienylmethylene)-1, 3-thiazolidine-2, 4-dione on HIV-1 reverse transcriptase: novel drug acting on enzyme

Bioinformation ◽

10.6026/97320630008678 ◽

2012 ◽

Vol 8 (14) ◽

pp. 678-683 ◽

Cited By ~ 5

Author(s):

Chandrabhan Seniya ◽

Ajay Yadav ◽

Kuldeep Uchadia ◽

Sanjay Kumar ◽

Nitin Sagar ◽

...

Keyword(s):

Molecular Docking ◽

Reverse Transcriptase ◽

Novel Drug ◽

Hiv 1

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MVA-B AS HIV/AIDS VACCINE CANDIDATE: FROM BASIC SCIENCE TO PROPHYLACTIC AND THERAPEUTIC CLINICAL TRIALS

Anales de la Real Academia Nacional de Farmacia ◽

10.53519/analesranf.2020.86.01.04 ◽

2020 ◽

pp. 29-60

Author(s):

Carmen Elena Gómez Rodríguez

Keyword(s):

Clinical Trials ◽

Vaccine Candidate ◽

Therapeutic Vaccine ◽

Basic Knowledge ◽

Antigen Delivery ◽

Modified Vaccinia Virus Ankara ◽

Hiv 1 ◽

Hiv Aids

The highly attenuated poxvirus strain modified vaccinia virus Ankara (MVA) has reached maturity as antigen delivery system and as a vaccine candidate against a broad spectrum of infectious diseases. This has been largely recognized from research on virus–host cell interactions, gene expression profiling, virus distribution and immunological studies in preclinical and clinical trials. This review includes our main contributions from the basic knowledge of the biology of the MVA vector, both in vitro and in vivo, in comparison with the attenuated NYVAC strain, to its evaluation as a vaccine candidate against HIV/AIDS in clinical trials. We will detail the generation and characterization of the recombinant poxvirus vector MVA expressing the HIV-1 Env, Gag, Pol and Nef antigens from clade B (referred as MVA-B) and review the preclinical data that supported the evaluation of MVA-B as the first in human HIV-1 prophylactic and therapeutic vaccine in Spain. In addition, we will assess the results of clinical trials and discuss the research projects we are currently working on considering the latest scientific advances in the HIV vaccine field.

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HIV-1 integrase is capable of targeting DNA to the nucleus via an Importin α/β-dependent mechanism

Biochemical Journal ◽

10.1042/bj20060466 ◽

2006 ◽

Vol 398 (3) ◽

pp. 475-484 ◽

Cited By ~ 73

Author(s):

Anna C. Hearps ◽

David A. Jans

Keyword(s):

Nuclear Import ◽

Nuclear Accumulation ◽

Viral Gene ◽

Intact Cells ◽

Vitro Assay ◽

In Vitro Techniques ◽

Hiv 1 ◽

Hiv Aids

In addition to its well-documented role in integration of the viral genome, the HIV-1 enzyme IN (integrase) is thought to be involved in the preceding step of importing the viral cDNA into the nucleus. The ability of HIV to transport its cDNA through an intact nuclear envelope allows HIV-1 to infect non-dividing cells, which is thought to be crucial for the persistent nature of HIV/AIDS. Despite this, the mechanism utilized by HIV-1 to import its cDNA into the nucleus, and the viral proteins involved, remains ill-defined. In the present study we utilize in vitro techniques to assess the nuclear import properties of the IN protein, and show that IN interacts with members of the Imp (Importin) family of nuclear transport proteins with high affinity and exhibits rapid nuclear accumulation within an in vitro assay, indicating that IN possesses potent nucleophilic potential. IN nuclear import appears to be dependent on the Imp α/β heterodimer and Ran GTP (Ran in its GTP-bound state), but does not require ATP. Importantly, we show that IN is capable of binding DNA and facilitating its import into the nucleus of semi-intact cells via a process that involves basic residues within amino acids 186–188 of IN. These results confirm IN as an efficient mediator of DNA nuclear import in vitro and imply the potential for IN to fulfil such a role in vivo. These results may not only aid in highlighting potential therapeutic targets for impeding the progression of HIV/AIDS, but may also be relevant for non-viral gene delivery.

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Comprehensive Cross-Clade Characterization of Antibody-Mediated Recognition, Complement-Mediated Lysis, and Cell-Mediated Cytotoxicity of HIV-1 Envelope-Specific Antibodies toward Eradication of the HIV-1 Reservoir

Journal of Virology ◽

10.1128/jvi.00634-17 ◽

2017 ◽

Vol 91 (16) ◽

Cited By ~ 15

Author(s):

Shariq Mujib ◽

Jun Liu ◽

A. K. M. Nur-ur Rahman ◽

Jordan A. Schwartz ◽

Phil Bonner ◽

...

Keyword(s):

T Cells ◽

Cd4 T Cells ◽

Neutralizing Antibodies ◽

Specific Antibodies ◽

Global Epidemic ◽

Infected Cells ◽

Hiv 1 ◽

Hiv Aids

ABSTRACT Immunotherapy with passive administration of broadly neutralizing HIV-1 envelope-specific antibodies (bnAbs) in the setting of established infection in vivo has yielded mixed results. The contribution of different antibodies toward the direct elimination of infected cells is poorly understood. In this study, we determined the ability of 12 well-characterized anti-HIV-1 neutralizing antibodies to recognize and eliminate primary CD4 T cells infected with HIV-1 belonging to clades A, B, C, and D, via antibody-dependent complement-mediated lysis (ADCML) and antibody-dependent cell-mediated cytotoxicity (ADCC), in vitro. We further tested unique combinations of these antibodies to determine the optimal antibody cocktails to be tested in future clinical trials. We report that antibody binding to infected CD4 T cells is highly variable and correlates with ADCML and ADCC processes. Particularly, antibodies targeting the envelope glycan shield (2G12) and V1/V2 site (PG9, PG16, and PGT145) are best at recognizing HIV-1-infected CD4 T cells. However, only PG9 and PG16 and their combinations with other bnAbs sufficiently induced the elimination of HIV-1-infected CD4 T cells by ADCML, ADCC, or both. Notably, CD4 binding site antibodies VRC01, 3BNC117, and NIH45-46 G54W did not exhibit recognition of infected cells and were unable to induce their killing. Future trials geared toward the development of a cure for HIV/AIDS should incorporate V1/V2 antibodies for maximal clearance of infected cells. With the use of only primary immune cells, we conducted a comprehensive cross-clade physiological analysis to aid the direction of antibodies as therapeutics toward the development of a cure for HIV/AIDS. IMPORTANCE Several antibodies capable of neutralizing the majority of circulating HIV-1 strains have been identified to date and have been shown to prevent infection in animal models. However, the use of combinations of such broadly neutralizing antibodies (bnAbs) for the treatment and eradication of HIV-1 in infected humans remains uncertain. In this study, we tested the ability of bnAbs to directly recognize and eliminate primary human CD4 T cells infected with diverse HIV-1 strains representative of the global epidemic by antibody-dependent pathways. We also tested several combinations of bnAbs in our assays in order to maximize the clearance of infected cells. We show that the ability of bnAbs to identify and kill infected cells is highly variable and that only a few of them are able to exert this function. Our data will help guide the formulation of bnAbs to test in future human trials aimed at the development of a cure.

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