Cnicin as an Anti-SARS-CoV-2: An Integrated In Silico and In Vitro Approach for the Rapid Identification of Potential COVID-19 Therapeutics.

Since the emergence of the SARS-CoV-2 pandemic in 2019, it has remained a significant global threat, especially with the newly evolved variants. Despite the presence of different COVID-19 vaccines, the discovery of proper antiviral therapeutics is an urgent necessity. Nature is considered as a historical trove for drug discovery, especially in global crises. During our efforts to discover potential anti-SARS CoV-2 natural therapeutics, screening our in-house natural products and plant crude extracts library led to the identification of C. benedictus extract as a promising candidate. To find out the main chemical constituents responsible for the extract's antiviral activity, we utilized recently reported SARS CoV-2 structural information in comprehensive in silico investigations (e.g., ensemble docking and physics-based molecular modeling). As a result, we constructed protein-protein and protein-compound interaction networks that suggest cnicin as the most promising anti-SARS CoV-2 hit that might inhibit viral multi-targets. The subsequent in vitro validation confirmed that cnicin could impede the viral replication of SARS CoV-2 in a dose-dependent manner, with an IC50 value of 1.18 µg/mL. Furthermore, drug-like property calculations strongly recommended cnicin for further in vivo and clinical experiments. The present investigation highlighted natural products as crucial and readily available sources for developing antiviral therapeutics. Additionally, it revealed the key contributions of bioinformatics and computer-aided modeling tools in accelerating the discovery rate of potential therapeutics, particularly in emergency times like the current COVID-19 pandemic.

Malaria and COVID-19: unmasking their ties.

The incidence and mortality of COVID-19, according to the World Health Organization reports, shows a noticeable difference between North America, Western Europe, and South Asia on one hand and most African countries on the other hand, especially the malaria-endemic countries. Although this observation could be attributed to limited testing capacity, mitigation tools adopted and cultural habits, many theories have been postulated to explain this difference in prevalence and mortality. Because death tends to occur more in elders, both the role of demography, and how the age structure of a population may contribute to the difference in mortality rate between countries were discussed. The variable distribution of the ACEI/D and the ACE2 (C1173T substitution) polymorphisms has been postulated to explain this variable prevalence. Up-to-date data regarding the role of hydroxychloroquine (HCQ) and chloroquine (CQ) in COVID-19 have been summarized. The article also sheds lights on how the similarity of malaria and COVID-19 symptoms can lead to misdiagnosis of one disease for the other or overlooking the possibility of co-infection. As the COVID-19 pandemic threatens the delivery of malaria services, such as the distribution of insecticide-treated nets (ITNs), indoor residual spraying, as well as malaria chemoprevention there is an urgent need for rapid and effective responses to avoid malaria outbreaks.