COVID-19 signalome: Potential therapeutic interventions.

Ángel Serrano-Aroca, Debmalya Barh, Murtaza M Tambuwala, Fuad M Alzahrani, Ibrahim F Halawani, Khalaf F Alsharif, Khalid J Alzahrani, Vasco Azevedo, Elrashdy M Redwan, Sk Sarif Hassan, Vladimir N Uversky, Kenneth Lundstrom, Lidiane Orlandi, Ana Cláudia B H Ferreira, Sara A Raslan, Mohamed Raslan, Eslam M Shehata, Nagwa A Sabri, Katarina Baralić, Alaa A A Aljabali, Esma Bilajac, Altijana Hromić-Jahjefendić

Journal: Cellular signalling 2023;103():110559

PMID: 36521656

Free Full Text on Elsevier Science View on PubMed

Abstract

The COVID-19 pandemic has triggered intensive research and development of drugs and vaccines against SARS-CoV-2 during the last two years. The major success was especially observed with development of vaccines based on viral vectors, nucleic acids and whole viral particles, which have received emergent authorization leading to global mass vaccinations. Although the vaccine programs have made a big impact on COVID-19 spread and severity, emerging novel variants have raised serious concerns about vaccine efficacy. Due to the urgent demand, drug development had originally to rely on repurposing of antiviral drugs developed against other infectious diseases. For both drug and vaccine development the focus has been mainly on SARS-CoV-2 surface proteins and host cell receptors involved in viral attachment and entry. In this review, we expand the spectrum of SARS-CoV-2 targets by investigating the COVID-19 signalome. In addition to the SARS-CoV-2 Spike protein, the envelope, membrane, and nucleoprotein targets have been subjected to research. Moreover, viral proteases have presented the possibility to develop different strategies for the inhibition of SARS-CoV-2 replication and spread. Several signaling pathways involving the renin-angiotensin system, angiotensin-converting enzymes, immune pathways, hypoxia, and calcium signaling have provided attractive alternative targets for more efficient drug development.

Address: PanTherapeutics, Route de Lavaux 49, CH1095 Lutry, Switzerland.; Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Hrasnicka Cesta 15, 71000 Sarajevo, Bosnia and Herzegovina.; Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Yarmouk University, P.O. Box 566, Irbid 21163, Jordan.; Department of Toxicology "Akademik Danilo Soldatović", University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia.; Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo 11865, Egypt.; Drug Research Center, Clinical Research and Bioanalysis Department, Cairo 11865, Egypt.; Campinas State University, Campinas, São Paulo, Brazil; University Center of Lavras (UNILAVRAS), Lavras, Minas Gerais, Brazil.; Biomaterials and Bioengineering Laboratory, Centro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia San Vicente Mártir, c/Guillem de Castro 94, 46001, Valencia, Spain.; Department of Molecular Medicine and USF Health Byrd Alzheimer's Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.; Department of Mathematics, Pingla Thana Mahavidyalaya, Maligram 721140, India.; Department of Biological Sciences, Faculty of Sciences, King Abdulaziz University, P.O. Box 80203, Jeddah, Saudi Arabia.; Department of Genetics, Ecology and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil.; Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.; Lincoln Medical School, University of Lincoln, Brayford Pool Campus, Lincoln LN6 7TS, UK.; Department of Genetics, Ecology and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil; Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur 721172, India. Electronic address: [email protected].

DOI: 10.1016/j.cellsig.2022.110559

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Medical:

https://medlineplus.gov/covid19coronavirusdisease2...

Miscellaneous:

https://assays.cancer.gov/CPTAC-438

MeSH Terms: Humans, COVID-19, SARS-CoV-2, COVID-19 Vaccines, Pandemics, Receptors, Virus, Antiviral Agents