Mannose-Binding Lectins as Potent Antivirals against SARS-CoV-2

Author:

Grosche Victória Riquena12ORCID,Souza Leandro Peixoto Ferreira3,Ferreira Giulia Magalhães1,Guevara-Vega Marco3,Carvalho Tamara2,Silva Romério Rodrigues dos Santos4ORCID,Batista Karla Lilian Rodrigues5,Abuna Rodrigo Paolo Flores67,Silva João Santana67ORCID,Calmon Marília de Freitas2ORCID,Rahal Paula2,da Silva Luis Cláudio Nascimento5ORCID,Andrade Bruno Silva8ORCID,Teixeira Claudener Souza4,Sabino-Silva Robinson3ORCID,Jardim Ana Carolina Gomes12ORCID

Affiliation:

1. Laboratory of Antiviral Research, Institute of Biomedical Science (ICBIM), Federal University of Uberlândia (UFU), Uberlândia 38405-317, Brazil

2. Institute of Biosciences, Languages, and Exact Sciences (Ibilce), São Paulo State University (Unesp), São José do Rio Preto 15054-000, Brazil

3. Innovation Center in Salivary Diagnostic and Nanobiotechnology, Institute of Biomedical Science (ICBIM), Federal University of Uberlândia (UFU), Uberlândia 38405-317, Brazil

4. Center of Agrarian Science and Biodiversity, Federal University of Cariri (UFCA), Crato 63130-025, Brazil

5. Laboratory of Microbial Pathogenesis, CEUMA University, São Luís 65045-380, Brazil

6. Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, Brazil

7. Oswaldo Cruz Foundation (Fiocruz), Bi-Institutional Platform for Translational Medicine, Ribeirão Preto 14049-900, Brazil

8. Laboratory of Bioinformatics and Computational Chemistry, State University of Southwest of Bahia, Jequié 45205-490, Brazil

Abstract

The SARS-CoV-2 entry into host cells is mainly mediated by the interactions between the viral spike protein (S) and the ACE-2 cell receptor, which are highly glycosylated. Therefore, carbohydrate binding agents may represent potential candidates to abrogate virus infection. Here, we evaluated the in vitro anti-SARS-CoV-2 activity of two mannose-binding lectins isolated from the Brazilian plants Canavalia brasiliensis and Dioclea violacea (ConBR and DVL). These lectins inhibited SARS-CoV-2 Wuhan-Hu-1 strain and variants Gamma and Omicron infections, with selectivity indexes (SI) of 7, 1.7, and 6.5, respectively for ConBR; and 25, 16.8, and 22.3, for DVL. ConBR and DVL inhibited over 95% of the early stages of the viral infection, with strong virucidal effect, and also protected cells from infection and presented post-entry inhibition. The presence of mannose resulted in the complete lack of anti-SARS-CoV-2 activity by ConBR and DVL, recovering virus titers. ATR-FTIR, molecular docking, and dynamic simulation between SARS-CoV-2 S and either lectins indicated molecular interactions with predicted binding energies of −85.4 and −72.0 Kcal/Mol, respectively. Our findings show that ConBR and DVL lectins possess strong activities against SARS-CoV-2, potentially by interacting with glycans and blocking virus entry into cells, representing potential candidates for the development of novel antiviral drugs.

Funder

CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior)—Brazil—Prevention and Combat of Outbreaks, Endemics, Epidemics and Pandemics

Minas Gerais Research Foundation

São Paulo Research Foundation

National Council for Scientific and Technological Development

National Institute of Science and Technology in Theranostics and Nanobiotechnology

FAPEMIG # #INCT TeraNano

CAPES

CNPq productivity fellowship

PrInt CAPES/UFU

PROPP-UFU

Publisher

MDPI AG

Subject

Virology,Infectious Diseases

Reference106 articles.

1. A Novel Coronavirus from Patients with Pneumonia in China, 2019;Zhu;N. Engl. J. Med.,2020

2. WHO Declares COVID-19 a Pandemic;Cucinotta;Acta Biomed.,2020

3. WHO (2023). WHO Coronavirus Disease (COVID-19) Dashboard, WHO.

4. Comparing COVID-19 Vaccines for Their Characteristics, Efficacy and Effectiveness against SARS-CoV-2 and Variants of Concern: A Narrative Review;Fiolet;Clin. Microbiol. Infect.,2022

5. From SARS to SARS-CoV-2, Insights on Structure, Pathogenicity and Immunity Aspects of Pandemic Human Coronaviruses;Kirtipal;Infect. Genet. Evol.,2020

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3