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Highly Specific Sigma Receptor Ligands Exhibit Anti-Viral Properties in SARS-CoV-2 Infected Cells.
Ostrov, David A; Bluhm, Andrew P; Li, Danmeng; Khan, Juveriya Qamar; Rohamare, Megha; Rajamanickam, Karthic; K Bhanumathy, Kalpana; Lew, Jocelyne; Falzarano, Darryl; Vizeacoumar, Franco J; Wilson, Joyce A; Mottinelli, Marco; Kanumuri, Siva Rama Raju; Sharma, Abhisheak; McCurdy, Christopher R; Norris, Michael H.
  • Ostrov DA; Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610, USA.
  • Bluhm AP; Department of Geography, University of Florida College of Liberal Arts and Sciences, Gainesville, FL 32611, USA.
  • Li D; Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610, USA.
  • Khan JQ; Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610, USA.
  • Rohamare M; Department of Biochemistry, Microbiology, and Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
  • Rajamanickam K; Department of Biochemistry, Microbiology, and Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
  • K Bhanumathy K; Division of Oncology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
  • Lew J; Division of Oncology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
  • Falzarano D; Vaccine and Infectious Disease Organization-International Vaccine Centre, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
  • Vizeacoumar FJ; Vaccine and Infectious Disease Organization-International Vaccine Centre, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
  • Wilson JA; Division of Oncology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
  • Mottinelli M; Cancer Research Department, Saskatchewan Cancer Agency, Saskatoon, SK S7N 5E5, Canada.
  • Kanumuri SRR; Department of Biochemistry, Microbiology, and Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
  • Sharma A; Department of Medicinal Chemistry, University of Florida College of Pharmacy, Gainesville, FL 32610, USA.
  • McCurdy CR; Department of Pharmaceutics, University of Florida College of Pharmacy, Gainesville, FL 32610, USA.
  • Norris MH; Translational Drug Development Core, University of Florida Clinical and Translational Sciences Institute, Gainesville, FL 32610, USA.
Pathogens ; 10(11)2021 Nov 20.
Article in English | MEDLINE | ID: covidwho-1524103
ABSTRACT
(1)

Background:

There is a strong need for prevention and treatment strategies for COVID-19 that are not impacted by SARS-CoV-2 mutations emerging in variants of concern. After virus infection, host ER resident sigma receptors form direct interactions with non-structural SARS-CoV-2 proteins present in the replication complex. (2)

Methods:

In this work, highly specific sigma receptor ligands were investigated for their ability to inhibit both SARS-CoV-2 genome replication and virus induced cellular toxicity. This study found antiviral activity associated with agonism of the sigma-1 receptor (e.g., SA4503), ligation of the sigma-2 receptor (e.g., CM398), and a combination of the two pathways (e.g., AZ66). (3)

Results:

Intermolecular contacts between these ligands and sigma receptors were identified by structural modeling. (4)

Conclusions:

Sigma receptor ligands and drugs with off-target sigma receptor binding characteristics were effective at inhibiting SARS-CoV-2 infection in primate and human cells, representing a potential therapeutic avenue for COVID-19 prevention and treatment.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Topics: Variants Language: English Year: 2021 Document Type: Article Affiliation country: Pathogens10111514

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Full text: Available Collection: International databases Database: MEDLINE Topics: Variants Language: English Year: 2021 Document Type: Article Affiliation country: Pathogens10111514