Antioxidant Capacity and Antimicrobial Activity of Commercial Samples of Guava Leaves (\u3cem\u3ePsidium guajava\u3c/em\u3e)

Psidium guajava is a small tree native to South and Central America. Guava leaves have traditionally been used for treating different illnesses. These benefits can be attributed to phenolics and flavonoids produced by guava. The chemical composition of guava leaf extracts was correlated with biological activity. Total phenolics, total flavonoids, ABTS/DPPH, TZM-bl, plaque reduction, XTT, spectrophotometric and Kirby-Bauer assays were used to test phenols, flavonoids, antioxidant properties, antiviral activity, cytotoxicity, and antibacterial activity, respectively. The median cytotoxicity concentration and half-maximal effective concentration values were obtained in order to determine antiviral selectivity against human immunodeficiency virus type 1 and herpes simplex virus type 1. Antibacterial activity against Escherichia coli and Bacillus subtilis were evaluated using a spectrophotometric assay and Kirby-Bauer test. The guava leaf extracts had a high phenol (0.8 to 2.1 GAE mg/mL) and flavonoid (62.7 to 182.1 Rutin Eq mg/g DW) content that correlated with high antioxidant capacity and selective antiviral activity (therapeutic index values above 10). Results of antibacterial tests indicated that the extracts have activity against gram-negative and gram-positive bacteria

Antioxidant, antibacterial, and anti-SARS-CoV Activity of Commercial Products of \u3cem\u3eXylopia\u3c/em\u3e (\u3cem\u3eXylopia aethiopica\u3c/em\u3e)

Xylopia aethiopica (Annonaceae) is a spice and medicinal plant that grows wild in many West African countries (from Liberia to Nigeria) and is locally known as Guinea pepper, grains of Selim, hwentia and uda. The dried fruits are used as a flavoring for soups and traditionally in decoctions as an analgesic and anti-inflammatory, as well as a treatment for infections. The medicinal properties of the fruits are associated with the presence of phenolics and essential oil constituents. We studied the total phenols, total flavonoids, and antioxidant activity in different X. aethiopica extracts using spectrophotometry. We found variation in total phenolic and flavonoids and antioxidant capacity between different samples and different extraction solvents. Antibacterial activity against Escherichia coli and Bacillus subtilis were evaluated using a spectrophotometric assay and Kirby-Bauer test. Additionally, a pseudoviral cell-based assay was used to test the antiviral activity against severe acute respiratory syndrome coronaviruses (SARS-CoV-1 and SARS-CoV-2). High total phenolic and flavonoid content was correlated with high antioxidant capacity. Results of antibacterial tests indicated that one Xylopia extract potentially has strong antibacterial activity against gram-positive bacteria B. subtilis. The pseudoviral assay showed moderate antiviral activity against SARS-CoV-1 and SARS-CoV-2

Results of a phase 1, randomized, placebocontrolled first-in-human trial of griffithsin formulated in a carrageenan vaginal gel

HIV pre-exposure prophylaxis (PrEP) is dominated by clinical therapeutic antiretroviral (ARV) drugs. Griffithsin (GRFT) is a non-ARV lectin with potent anti-HIV activity. GRFT’s preclinical safety, lack of systemic absorption after vaginal administration in animal studies, and lack of cross-resistance with existing ARV drugs prompted its development for topical HIV PrEP. We investigated safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of PC-6500 (0.1% GRFT in a carrageenan (CG) gel) in healthy women after vaginal administration. This randomized, placebo-controlled, parallel group, double-blind first-in-human phase 1 study enrolled healthy, HIV-negative, non-pregnant women aged 24–45 years. In the open label period, all participants (n = 7) received single dose of PC- 6500. In the randomized period, participants (n = 13) were instructed to self-administer 14 doses of PC-6500 or its matching CG placebo (PC-535) once daily for 14 days. The primary outcomes were safety and PK after single dose, and then after 14 days of dosing. Exploratory outcomes were GRFT concentrations in cervicovaginal fluids, PD, inflammatory mediators and gene expression in ectocervical biopsies. This trial is registered with ClinicalTrials. gov, number NCT02875119. No significant adverse events were recorded in clinical or laboratory results or histopathological evaluations in cervicovaginal mucosa, and no anti-drug (GRFT) antibodies were detected in serum. No cervicovaginal proinflammatory responses and no changes in the ectocervical transcriptome were evident. Decreased levels of proinflammatory chemokines (CXCL8, CCL5 and CCL20) were observed. GRFT was not detected in plasma. GRFT and GRFT/CG in cervicovaginal lavage samples inhibited HIV and HPV, respectively, in vitro in a dose-dependent fashion. These data suggest GRFT formulated in a CG gel is a safe and promising on-demand multipurpose prevention technology product that warrants further investigation

Antiviral activity of aframomum melegueta against severe acute respiratory syndrome coronaviruses type 1 and 2

Plant-based compounds with antiviral properties against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been identified in Aframomum melegueta through computational models. The seed extract have been traditionally used to treat different illnesses. In this study, ethanolic extracts were prepared for six commercial samples of A. melegueta seeds. Antiviral activity was tested using the XTT cytotoxicity assay and cell-based SARS-CoV-1 and 2 pseudoviral models. The presence of gingerols and other non-volatile components in the seed extracts was determined using an Agilent 1290 UPLC/DAD in tandem with an Agilent 6546 QTOF-MS. Our results showed selective antiviral activity with TI values as high as 13.1. Fifteen gingerols were identified by chromatographic analysis, with 6-gingerol being the dominant component in each seed extract. A combination of 6-gingerol with techtochrysin, previously identified in computational models as a potential active ingredient against SARS-CoV-2, demonstrated additive antiviral activity with CI values between 0.8715 and 0.9426. We confirmed the antiviral activity of A. melegueta predicted through computational models and identified a different compound, 6-gingerol, as a potential active ingredient

Antioxidant capacity and antimicrobial activity of commercial samples of guava leaves

Psidium guajava is a small tree native to South and Central America. Guava leaves have traditionally been used for treating different illnesses. These benefits can be attributed to phenolics and flavonoids produced by guava. The chemical composition of guava leaf extracts was correlated with biological activity. Total phenolics, total flavonoids, ABTS/DPPH, TZM-bl, plaque reduction, XTT, spectrophotometric and Kirby-Bauer assays were used to test phenols, flavonoids, antioxidant properties, antiviral activity, cytotoxicity, and antibacterial activity, respectively. The median cytotoxicity concentration and half-maximal effective concentration values were obtained in order to determine antiviral selectivity against human immunodeficiency virus type 1 and herpes simplex virus type 1. Antibacterial activity against Escherichia coli and Bacillus subtilis were evaluated using a spectrophotometric assay and Kirby-Bauer test. The guava leaf extracts had a high phenol (0.8 to 2.1 GAE mg/mL) and flavonoid (62.7 to 182.1 Rutin Eq mg/g DW) content that correlated with high antioxidant capacity and selective antiviral activity (therapeutic index values above 10). Results of antibacterial tests indicated that the extracts have activity against gram-negative and gram-positive bacteria

Griffithsin and carrageenan combination results in antiviral synergy against SARS-CoV-1 and 2 in a pseudoviral model

Over 182 million confirmed cases of COVID-19 and more than 4 million deaths have been reported to date around the world. It is essential to identify broad-spectrum antiviral agents that may prevent or treat infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but also by other coronaviruses that may jump the species barrier in the future. We evaluated the antiviral selectivity of griffithsin and sulfated and non-sulfated polysaccharides against SARS-CoV-1 and SARS-CoV-2 using a cytotoxicity assay and a cell-based pseudoviral model. The half-maximal cytotoxic concentration (CC50) and half-maximal effective concentration (EC50) were determined for each compound, using a dose-response-inhibition analysis on GraphPad Prism v9.0.2 software (San Diego, CA, USA). The therapeutic index (TI = CC50/EC50) was calculated for each compound. The potential synergistic, additive, or antagonistic effect of different compound combinations was determined by CalcuSyn v1 software (Biosoft, Cambridge, UK), which estimated the combination index (CI) values. Iota and lambda carrageenan showed the most potent antiviral activity (EC50 between 3.2 and 7.5 µg/mL). Carrageenan and griffithsin combinations exhibited synergistic activity (EC50 between 0.2 and 3.8 µg/mL; combination index \u3c 1), including against recent SARS-CoV-2 mutations. The griffithsin and carrageenan combination is a promising candidate to prevent or treat infections by SARS-CoV-1 and SARS-CoV-2

Results of a phase 1, randomized, placebo controlled first-in-human trial of griffithsin formulated in a carrageenan vaginal gel

HIV pre-exposure prophylaxis (PrEP) is dominated by clinical therapeutic antiretroviral (ARV) drugs. Griffithsin (GRFT) is a non-ARV lectin with potent anti-HIV activity. GRFT\u27s preclinical safety, lack of systemic absorption after vaginal administration in animal studies, and lack of cross-resistance with existing ARV drugs prompted its development for topical HIV PrEP. We investigated safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of PC-6500 (0.1% GRFT in a carrageenan (CG) gel) in healthy women after vaginal administration. This randomized, placebo-controlled, parallel group, double-blind first-in-human phase 1 study enrolled healthy, HIV-negative, non-pregnant women aged 24-45 years. In the open label period, all participants (n = 7) received single dose of PC- 6500. In the randomized period, participants (n = 13) were instructed to self-administer 14 doses of PC-6500 or its matching CG placebo (PC-535) once daily for 14 days. The primary outcomes were safety and PK after single dose, and then after 14 days of dosing. Exploratory outcomes were GRFT concentrations in cervicovaginal fluids, PD, inflammatory mediators and gene expression in ectocervical biopsies. This trial is registered with ClinicalTrials. gov, number NCT02875119. No significant adverse events were recorded in clinical or laboratory results or histopathological evaluations in cervicovaginal mucosa, and no anti-drug (GRFT) antibodies were detected in serum. No cervicovaginal proinflammatory responses and no changes in the ectocervical transcriptome were evident. Decreased levels of proinflammatory chemokines (CXCL8, CCL5 and CCL20) were observed. GRFT was not detected in plasma. GRFT and GRFT/CG in cervicovaginal lavage samples inhibited HIV and HPV, respectively, in vitro in a dose-dependent fashion. These data suggest GRFT formulated in a CG gel is a safe and promising on-demand multipurpose prevention technology product that warrants further investigation