The spike (S) protein of SARS-CoV-2 is a molecular target of great interest for developing drug therapies against COVID-19 because S is responsible for the interaction of the virus with the host cell receptor. Currently, there is no outpatient safety treatment for COVID-19 disease. Furthermore, we consider it of worthy importance to evaluate experimentally the possible interaction of drugs (approved by the Food and Drug Administration) and the S, considering some previously in silico and clinical use. Then, the objective of this study was to demonstrate the in vitro interaction of ivermectin with S. The equilibrium dialysis technique with UV-Vis was performed to obtain the affinity and dissociation constants. In addition, the Drug Affinity Responsive Target Stability (DARTS) technique was used to demonstrate the in vitro interaction of S with ivermectin. The results indicate the interaction between ivermectin and the S with an association and dissociation constant of Ka = 1.22 µM and Kd = 0.81 µM, respectively. The interaction was demonstrated in ratios of 1:50 pmol and 1:100 pmol (S: ivermectin) by the DARTS technique. The results obtained with these two different techniques demonstrate an interaction between S and ivermectin previously explored in silico, suggesting its clinical uses to stop the viral spread among susceptible human hosts.
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http://dx.doi.org/10.3390/ijms242216392 | DOI Listing |
Mol Biol Res Commun
January 2025
Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
The recent pernicious COVID-19 pandemic is caused by SARS-CoV-2. While most therapeutic strategies have focused on the viral spike protein, Open Reading Frame 8 (ORF8) plays a critical role in causing the severity of the disease. Nonetheless, there still needs to be more information on the ORF8 binding epitopes and their appropriate safe inhibitors.
View Article and Find Full Text PDFEPMA J
December 2024
Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan, Shandong 250117 People's Republic of China.
Int J Mol Sci
November 2024
Department of Biochemistry and Microbiology, University of Zululand, Kwa-Dlangezwa 3886, South Africa.
The spread of SARS-CoV-2 has led to an interest in using ivermectin (a potent antiparasitic agent) as an antiviral agent despite the lack of convincing in vivo clinical data for its use against COVID-19. The off-target prophylactic use of ivermectin adds a substantial risk of drug-drug interactions with pharmaceutical medications used to treat chronic conditions like diabetes and hypertension (metformin and hydrochlorothiazide, respectively). Therefore, this study aims to evaluate the potential drug-drug interactions between ivermectin with either metformin or hydrochlorothiazide.
View Article and Find Full Text PDFEpilepsia Open
November 2024
Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Onchocerciasis, commonly known as river blindness, is a neglected tropical disease caused by the parasite Onchocerca volvulus. It can lead to blindness and visual impairment. Studies have also demonstrated a link between onchocerciasis and epilepsy, with there being a correlation between onchocerciasis endemicity and epilepsy prevalence.
View Article and Find Full Text PDFEnviron Pollut
January 2025
Department of Pharmacy, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, China. Electronic address:
Avermectin B1a, a widely used pesticide, has recently raised safety concerns since it possesses potential cytotoxicity toward mammalian cells. Nevertheless, the exact mechanisms that underlie the cytotoxicity induced by avermectin B1a remain elusive. The loading of the mini-chromosome maintenance 6 protein (MCM6) onto chromatin at replication origins by chromatin licensing and DNA replication factor 1 (CDT1) is an essential step for licensing DNA for replication.
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