University of Louisville
Grade Level at Time of Presentation
Senior
Major
Neuroscience
Minor
Public Health
KY House District #
4
KY Senate District #
24
Faculty Advisor/ Mentor
Kenneth Palmer, PhD; Nobuyuki Matoba, PhD; Elizabeth Cash, PhD
Department
Department of Pharmacology and Toxicology
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible virus that causes acute respiratory disease with possible long-term complications, known as coronavirus disease 2019 (COVID-19). Griffithsin (GRFT; including the oxidation-resistant variant Q-GRFT used in this study) is an algal carbohydrate-binding protein exhibiting antiviral effects against many enveloped viruses, including all major variants of SARS- CoV-2 reported to date. Q-GRFT has been recombinantly manufactured in Nicotiana benthamiana plants, thoroughly purified, and formulated as an intranasal spray designed to be developed as a non-vaccine broad-spectrum prophylactic product for acute use. This is the first-in-human, randomized, double-blind, placebo-controlled study. The aims were to assess safety, tolerability, and pharmacokinetics of a single 3 mg dose of Q-GRFT. A total of eighteen healthy adult volunteers (aged 24-54 years; twelve Q-GRFT product, six placebo) were recruited. Mucosal and plasma Q-GRFT concentrations were measured by ELISA . Participants completed a Brief Smell Identification Test (BSIT) and a general quality of life assessment questionnaire (SF-12). The surveys showed no impact on quality of life or sense of smell in both active and placebo groups. The pharmacokinetic data indicates that Q-GRFT administered intranasally maintained quantifiable levels (>15 ng/mL) in nasal passages and the nasopharynx for up to 24 hours, while the drug substance was rapidly cleared from the oropharyngeal mucosa after 1 hour. There was no indication of systemic absorption or distribution of Q-GRFT. In vitromicroneutralization assays using nasopharyngeal swab samples suggested that Q-GRFT product significantly boosted anti-SARS-CoV-2 activity in the nasopharynx for up to 6 hours. The results support proceeding to a repeat dose trial in healthy volunteers. Commercialization of such a product provides a new means for immediate protection against SARS-CoV-2 infection, which would be beneficial for front-line healthcare workers, first responders, and other vulnerable populations with weakened immune systems.
Included in
Immune System Diseases Commons, Immunity Commons, Medicinal Chemistry and Pharmaceutics Commons, Pharmacology Commons, Respiratory Tract Diseases Commons, Toxicology Commons, Virus Diseases Commons
Phase 1A Clinical Study for Q-Griffithsin Intranasal Spray for Prevention of Coronavirus
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible virus that causes acute respiratory disease with possible long-term complications, known as coronavirus disease 2019 (COVID-19). Griffithsin (GRFT; including the oxidation-resistant variant Q-GRFT used in this study) is an algal carbohydrate-binding protein exhibiting antiviral effects against many enveloped viruses, including all major variants of SARS- CoV-2 reported to date. Q-GRFT has been recombinantly manufactured in Nicotiana benthamiana plants, thoroughly purified, and formulated as an intranasal spray designed to be developed as a non-vaccine broad-spectrum prophylactic product for acute use. This is the first-in-human, randomized, double-blind, placebo-controlled study. The aims were to assess safety, tolerability, and pharmacokinetics of a single 3 mg dose of Q-GRFT. A total of eighteen healthy adult volunteers (aged 24-54 years; twelve Q-GRFT product, six placebo) were recruited. Mucosal and plasma Q-GRFT concentrations were measured by ELISA . Participants completed a Brief Smell Identification Test (BSIT) and a general quality of life assessment questionnaire (SF-12). The surveys showed no impact on quality of life or sense of smell in both active and placebo groups. The pharmacokinetic data indicates that Q-GRFT administered intranasally maintained quantifiable levels (>15 ng/mL) in nasal passages and the nasopharynx for up to 24 hours, while the drug substance was rapidly cleared from the oropharyngeal mucosa after 1 hour. There was no indication of systemic absorption or distribution of Q-GRFT. In vitromicroneutralization assays using nasopharyngeal swab samples suggested that Q-GRFT product significantly boosted anti-SARS-CoV-2 activity in the nasopharynx for up to 6 hours. The results support proceeding to a repeat dose trial in healthy volunteers. Commercialization of such a product provides a new means for immediate protection against SARS-CoV-2 infection, which would be beneficial for front-line healthcare workers, first responders, and other vulnerable populations with weakened immune systems.