No abstract

In 2019, coronavirus has made the third apparition in the form of SARS-CoV-2, a novel strain of coronavirus that is extremely pathogenic and it uses the same receptor as SARS-CoV, the angiotensin-converting enzyme 2 (ACE2). However, more than 182 vaccine candidates have been announced; and 12 vaccines have been approved for use, although, even vaccinated individuals are still vulnerable to infection. In this study, we investigated PHELA, recognized as an herbal combination of four exotic African medicinal plants namely; Clerodendrum glabrum E. Mey. Lamiaceae, Gladiolus dalenii van Geel, Rotheca myricoides (Hochst.) Steane & Mabb, and Senna occidentalis (L.) Link; as a candidate therapy for COVID-19. In vitro testing found that PHELA inhibited > 90% of SARS-CoV-2 and SARS-CoV infection at concentration levels of 0.005 mg/ml to 0.03 mg/ml and close to 100% of MERS-CoV infection at 0.1 mg/ml to 0.6 mg/ml. The in vitro average IC50 of PHELA on SARS-COV-2, SARS-CoV and MERS-COV were ~ 0.01 mg/ml. Secondly in silico docking studies of compounds identified in PHELA showed very strong binding energy interactions with the SARS-COV-2 proteins. Compound 5 showed the highest affinity for SARS-COV-2 protein compared to other compounds with the binding energy of − 6.8 kcal mol−1. Our data showed that PHELA has potential and could be developed as a COVID-19 therapeutic.

HIV-1 infection is caused by cell-free and cell-associated viruses. Currently most of the assays used to screen potential HIV-1 entry inhibitors focus on the inhibition of cell-free viruses. One assay that is widely employed is the TZM-bl neutralization assay that uses pseudotyped viruses. However, a study by Abela et al. showed that many inhibitors that potently inhibit cell-free HIV-1 in this assay can be less effective against the cell-to-cell transmission of the virus. These researchers then designed a method to screen entry inhibitors for activity against cell-associated HIV-1, using pseudotyped viruses. The main limitation of this method, however, was that it can only be reliably employed against viruses that cannot infect target cells as cell-free virion in the absence of a polycation supplement such as DEAE (diethylaminoethyl). Thus, in the current study we provide modifications to this method that solves the problem and makes it possible to study entry inhibitors against cell-to-cell infection of both polycation depend and independent viruses. The main modification involves the introduction of the relative light unit (RLU) vs. virus producing 293-T cells / corresponding supernatants graph. This graph is used to select a virus input that only allows for the detection of cell-associated viruses infection. The method is a modification of the cell-to-cell transmission assay published by Abela et al. The method allows for the study of the inhibition of cell-to-cell transmission of both polycation dependent and independent HIV-1 pseudoviruses.