The H163A mutation unravels an oxidized conformation of the SARS-CoV-2 main protease DOI Creative Commons

Norman Tran,

Sathish Dasari, Sarah Barwell

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 12, 2023

Abstract The main protease of SARS-CoV-2 (Mpro) is an important target for developing COVID-19 therapeutics. Recent work has highlighted Mpro’s susceptibility to undergo redox-associated conformational changes in response cellular and immune-system-induced oxidation. Despite structural evidence indicating large-scale rearrangements upon oxidation, the mechanisms change its functional consequences are poorly understood. Here, we present crystal structure Mpro point mutant (H163A) that shows oxidized conformation with catalytic cysteine a disulfide bond. We hypothesize adopts this under oxidative stress protect against over-oxidation. Our metadynamics simulations illustrate potential mechanism by which H163 modulates transition suggest equilibrium exists wild type enzyme. show other mutations also significantly shift towards state altering free energies. Unique avenues research can be explored understanding how equilibrium.

Language: Английский

Withania somnifera (L.) Dunal (Ashwagandha): A comprehensive review on ethnopharmacology, pharmacotherapeutics, biomedicinal and toxicological aspects DOI Open Access
Subhabrata Paul,

Shreya Chakraborty,

Uttpal Anand

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 143, P. 112175 - 112175

Published: Sept. 27, 2021

Withania somnifera (L.) Dunal (Solanaceae) has been used as a traditional Rasayana herb for long time. Traditional uses of this plant indicate its ameliorative properties against plethora human medical conditions, viz. hypertension, stress, diabetes, asthma, cancer etc. This review presents comprehensive summary the geographical distribution, use, phytochemistry, and pharmacological activities W. active constituents. In addition, it detailed account presence an constituent in many commercial preparations with curative health benefits. Clinical studies toxicological considerations extracts constituents are also elucidated. Comparative analysis relevant in-vitro, in-vivo, clinical investigations indicated potent bioactivity phytochemicals anti-cancer, anti-inflammatory, apoptotic, immunomodulatory, antimicrobial, anti-diabetic, hepatoprotective, hypoglycaemic, hypolipidemic, cardio-protective spermatogenic agents. was found to be especially neurological psychological conditions like Parkinson's disease, Alzheimer's Huntington's ischemic stroke, sleep deprivation, amyotrophic lateral sclerosis, attention deficit hyperactivity disorder, bipolar anxiety, depression, schizophrenia obsessive-compulsive disorder. The probable mechanism action that imparts potential explored. However, in-depth needed on use diseases. Besides, is performed safe efficacious preclinical health-promoting herb.

Language: Английский

Citations

185

Occurrence, transformation, bioaccumulation, risk and analysis of pharmaceutical and personal care products from wastewater: a review DOI Creative Commons

Uttpal Anand,

Bashir Adelodun, Carlo Cabreros

et al.

Environmental Chemistry Letters, Journal Year: 2022, Volume and Issue: 20(6), P. 3883 - 3904

Published: Aug. 17, 2022

Abstract Almost all aspects of society from food security to disease control and prevention have benefited pharmaceutical personal care products, yet these products are a major source contamination that ends up in wastewater ecosystems. This issue has been sharply accentuated during the coronavirus pandemic 2019 (COVID-19) due higher use disinfectants other products. Here we review with focus on their occurrence environment, detection, risk, removal.

Language: Английский

Citations

110

SARS-CoV-2 and other pathogens in municipal wastewater, landfill leachate, and solid waste: A review about virus surveillance, infectivity, and inactivation DOI Open Access

Uttpal Anand,

Xuan Li, Sunita Kumari

et al.

Environmental Research, Journal Year: 2021, Volume and Issue: 203, P. 111839 - 111839

Published: Aug. 4, 2021

Language: Английский

Citations

105

Safer plant-based nanoparticles for combating antibiotic resistance in bacteria: A comprehensive review on its potential applications, recent advances, and future perspective DOI Creative Commons

Uttpal Anand,

María Carpena, Monika Kowalska‐Góralska

et al.

The Science of The Total Environment, Journal Year: 2022, Volume and Issue: 821, P. 153472 - 153472

Published: Jan. 29, 2022

Antibiotic resistance is one of the current threats to human health, forcing use drugs that are more noxious, costlier, and with low efficiency. There several causes behind antibiotic resistance, including over-prescription antibiotics in both humans livestock. In this scenario, researchers shifting new alternatives fight back concerning situation.

Language: Английский

Citations

82

Betelvine (Piper betleL.): A comprehensive insight into its ethnopharmacology, phytochemistry, and pharmacological, biomedical and therapeutic attributes DOI

Protha Biswas,

Uttpal Anand,

Suchismita Chatterjee Saha

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2022, Volume and Issue: 26(11), P. 3083 - 3119

Published: May 2, 2022

Piper betle L. (synonym: betel Blanco), or vine, an economically and medicinally important cash crop, belongs to the family Piperaceae, often known as green gold. The plant can be found all over world is cultivatedprimarily in South East Asian countries for its beautiful glossy heart-shaped leaves, which are chewed consumed betelquidand widely used Chinese Indian folk medicine, carminative, stimulant,astringent, against parasitic worms, conjunctivitis, rheumatism, wound, etc., andis also religious purposes. Hydroxychavicol most bioactive compound among wide range of phytoconstituents essential oil extracts. pharmacological attributes P. antiproliferation, anticancer, neuropharmacological, analgesic, antioxidant, antiulcerogenic, hepatoprotective, antifertility, antibacterial, antifungal many more. Immense attention has been paid nanoformulations their applications. application did not show cytotoxicity preclinical experiments, suggesting that it could serve a promising therapeutic candidate different diseases. present review comprehensively summarizes botanical description, geographical distribution, economic value cultivation, ethnobotanical uses, properties with insights toxicological, clinical efficacy, safety betle. findings suggest represents orally active safe natural agent exhibits great potential managing various human medical conditions. However, further research needed elucidate underlying molecular mechanisms action, aspects, structure-activity relationships, bioavailability synergistic interactions other drugs.

Language: Английский

Citations

73

A focused review on technologies, mechanisms, safety, and efficacy of available COVID-19 vaccines DOI Open Access
Parisa Ghasemiyeh, Soliman Mohammadi‐Samani, Negar Firouzabadi

et al.

International Immunopharmacology, Journal Year: 2021, Volume and Issue: 100, P. 108162 - 108162

Published: Sept. 17, 2021

Language: Английский

Citations

88

Differences in Clinical Characteristics Between Delta Variant and Wild-Type SARS-CoV-2 Infected Patients DOI Creative Commons

Zhenkui Hu,

Xing Huang, Jianguo Zhang

et al.

Frontiers in Medicine, Journal Year: 2022, Volume and Issue: 8

Published: Jan. 3, 2022

Background: As delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevailed in the current disease 2019 (COVID-19) pandemic, its clinical characteristics with difference from those wild-type strains have been little studied. Methods: We reported one cohort 341 patients COVID-19 admitted at Wuhan, China 2020 and other 336 Yangzhou, 2021, comparisons their demographic information, medical history, manifestation, hematological data. Furthermore, within cohort, none, partial, full vaccination were also compared to assess vaccine effectiveness. Findings: For a total 677 included this study, median age was 53.0 years [interquartile range (IQR): 38.0-66.0] 46.8% men. No found age, gender, percentage leading comorbidity between cohorts, but showed lessened time interval onset hospitalization, reduced portion smoking lowered frequency symptoms. parameters, most values demonstrated significant differences while rather than partial alleviated condition. This reflected viremic effect when succeeds or fails protect. Interpretation: Delta SARS-CoV-2 may cause profiles, timely diagnosis could protect worsened progression.

Language: Английский

Citations

60

Microbial strategies for degradation of microplastics generated from COVID-19 healthcare waste DOI Open Access
Satarupa Dey,

Uttpal Anand,

Vineet Kumar

et al.

Environmental Research, Journal Year: 2022, Volume and Issue: 216, P. 114438 - 114438

Published: Sept. 28, 2022

Language: Английский

Citations

55

COVID-19 vaccine hesitancy and acceptance: a comprehensive scoping review of global literature DOI Open Access
Umair Majid, Mobeen Ahmad,

Shahzadi Zain

et al.

Health Promotion International, Journal Year: 2022, Volume and Issue: 37(3)

Published: June 1, 2022

As countries continue the third year of pandemic, we believe that there has been unfair attention to COVID-19 vaccine efficacy and safety, while tacitly ignoring serious challenges with uptake, without which vaccination may not be effective against spread COVID-19. While several studies have published on hesitancy, remains a need conduct comprehensive global analysis hesitancy. We conducted scoping review 60 globally hesitancy acceptance. qualitative identify motivators barriers across cultural demographic contexts. found following factors relevant in any discussion about addressing or minimizing hesitancy: risk perceptions, trust health care systems, solidarity, previous experiences vaccines, misinformation, concerns side effects political ideology. combine our insights from this literature offer an important practical two strategies used improve uptake: (i) communication education (ii) rollout logistics.

Language: Английский

Citations

53

Translational aspect in peptide drug discovery and development: An emerging therapeutic candidate DOI Creative Commons

Uttpal Anand,

Anustup Bandyopadhyay,

Niraj Kumar Jha

et al.

BioFactors, Journal Year: 2022, Volume and Issue: 49(2), P. 251 - 269

Published: Nov. 3, 2022

Abstract In the last two decades, protein–protein interactions (PPIs) have been used as main target for drug development. However, with larger or superficial binding sites, it has extremely difficult to disrupt PPIs small molecules. On other hand, intracellular cannot be targeted by antibodies that penetrate cell membrane. Peptides a combination of conformational rigidity and flexibility can interfaces appropriate affinity specificity. Since introduction insulin nearly century ago, more than 80 peptide drugs approved treat variety diseases. These include deadly diseases such cancer human immunodeficiency virus infection. It is also useful against diabetes, chronic pain, osteoporosis. Today, research being done on these lessons learned from earlier approaches, which are still valid today, complement newer approaches display libraries. At same time, integrated genomics libraries new strategies open avenues discovery. The purpose this review examine problems in elucidating peptide‐protein recognition mechanism. This important develop peptide‐based interventions interfere endogenous protein interactions. New developed improve specificity existing agents potentially drugs. We highlight key challenges must overcome development realize their potential provide an overview recent trends addition, we take in‐depth look at early efforts hormone discovery, smart medicinal chemistry design, natural drugs, breakthrough advances molecular biology chemistry.

Language: Английский

Citations

41