Evaluation of Annona muricata Acetogenins as Potential Anti-SARS-CoV-2 Agents Through Computational Approaches.

Annona muricata, a tropical plant which has been extensively used in ethnomedicine to treat a wide range of diseases, from malaria to cancer. Interestingly, this plant has been reported to demonstrate significant antiviral properties against the human immunodeficiency virus, herpes simplex virus, human papilloma virus, hepatitis C virus and dengue virus. Additionally, the bioactive compounds responsible for antiviral efficacy have also shown to be selectively cytotoxic while inhibiting tumorigenic cell growth without affecting the normal cell growth. Annonaceous Acetogenins are a class of bioactive compounds exclusive to the Annonaceae family at which the plant A. muricata belongs. In the current study, we have created a library of Acetogenins unique to the plant, comprising of Annomuricin A, Annomuricin B, Annomuricin C, Muricatocin C, Muricatacin, cis-Annonacin, Annonacin-10-one, cis-Goniothalamicin, Arianacin and Javoricin, for in silico and theoretical evaluations against the SARS-CoV-2 spike protein in an attempt toward promotion of plant based drug development for the current pandemic of coronavirus disease 2019 (COVID-19). We found that all the Acetogenins showing in silico spike protein significantly docking with good binding affinities. Moreover, we envision A. muricata Acetogenins can be further studied by in vitro and in vivo models to identify potential anti-SARS-CoV-2 agents.

Biological characteristics and biomarkers of novel SARS-CoV-2 facilitated rapid development and implementation of diagnostic tools and surveillance measures.

Existing coronavirus named as a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has speeded its spread across the globe immediately after emergence in China, Wuhan region, at the end of the year 2019. Different techniques, including genome sequencing, structural feature classification by electron microscopy, and chest imaging using computed tomography, are primarily used to diagnose and screen SARS-CoV-2 suspected individuals. Determination of the viral structure, surface proteins, and genome sequence has provided a design blueprint for the diagnostic investigations of novel SARS-CoV-2 virus and rapidly emerging diagnostic technologies, vaccine trials, and cell-entry-inhibiting drugs. Here, we describe recent understandings on the spike glycoprotein (S protein), receptor-binding domain (RBD), and angiotensin-converting enzyme 2 (ACE2) and their receptor complex. This report also aims to review recently established diagnostic technologies and developments in surveillance measures for SARS-CoV-2 as well as the characteristics and performance of emerging techniques. Smartphone apps for contact tracing can help nations to conduct surveillance measures before a vaccine and effective medicines become available. We also describe promising point-of-care (POC) diagnostic technologies that are under consideration by researchers for advancement beyond the proof-of-concept stage. Developing novel diagnostic techniques needs to be facilitated to establish automatic systems, without any personal involvement or arrangement to curb an existing SARS-CoV-2 epidemic crisis, and could also be appropriate for avoiding the emergence of a future epidemic crisis.

In silico evaluation of flavonoids as effective antiviral agents on the spike glycoprotein of SARS-CoV-2.

The novel coronavirus pandemic has spread over in 213 countries as of July 2020. Approximately 12 million people have been infected so far according to the reports from World Health Organization (WHO). Preventive measures are being taken globally to avoid the rapid spread of virus. In the current study, an in silico approach is carried out as a means of inhibiting the spike protein of the novel coronavirus by flavonoids from natural sources that possess both antiviral and anti-inflammatory properties. The methodology is focused on molecular docking of 10 flavonoid compounds that are docked with the spike protein of SARS-CoV-2, to determine the highest binding affinity at the binding site. Molecular dynamics simulation was carried out with the flavonoid-protein complex showing the highest binding affinity and highest interactions. The flavonoid naringin showed the least binding energy of -9.8 Kcal/mol with the spike protein which was compared with the standard drug, dexamethasone which is being repurposed to treat critically ill patients. MD simulation was carried out on naringin-spike protein complex for their conformational stability in the active site of the novel coronavirus spike protein. The RMSD of the complex appeared to be more stable when compared to that of the protein from 0.2 nm to 0.4 nm. With the aid of this in silico approach further in vitro studies can be carried out on these flavonoids against the novel coronavirus as a means of viral protein inhibitors.