In-silico approaches for identification of compounds inhibiting SARS-CoV-2 3CL protease.

The world has witnessed of many pandemic waves of SARS-CoV-2. However, the incidence of SARS-CoV-2 infection has now declined but the novel variant and responsible cases has been observed globally. Most of the world population has received the vaccinations, but the immune response against COVID-19 is not long-lasting, which may cause new outbreaks. A highly efficient pharmaceutical molecule is desperately needed in these circumstances. In the present study, a potent natural compound that could inhibit the 3CL protease protein of SARS-CoV-2 was found with computationally intensive search. This research approach is based on physics-based principles and a machine-learning approach. Deep learning design was applied to the library of natural compounds to rank the potential candidates. This procedure screened 32,484 compounds, and the top five hits based on estimated pIC50 were selected for molecular docking and modeling. This work identified two hit compounds, CMP4 and CMP2, which exhibited strong interaction with the 3CL protease using molecular docking and simulation. These two compounds demonstrated potential interaction with the catalytic residues His41 and Cys154 of the 3CL protease. Their calculated binding free energies to MMGBSA were compared to those of the native 3CL protease inhibitor. Using steered molecular dynamics, the dissociation strength of these complexes was sequentially determined. In conclusion, CMP4 demonstrated strong comparative performance with native inhibitors and was identified as a promising hit candidate. This compound can be applied in-vitro experiment for the validation of its inhibitory activity. Additionally, these methods can be used to identify new binding sites on the enzyme and to design new compounds that target these sites.

COVID-19 Vaccine Acceptance: Beliefs and Barriers Associated with Vaccination Among the Residents of KSA.

INTRODUCTION: COVID-19 was declared a pandemic in March 2020 by the World Health Organization. Control of COVID-19 depends on the potential vaccine and its successful delivery to a large portion of the population to develop herd immunity. All the governments have made a robust plan to distribute the vaccine to their people, but many countries could not achieve adequate vaccination coverage. Hence, this study explores people's beliefs and barriers to vaccination and provides valuable inputs to the government to attain adequate vaccination. OBJECTIVE: To know the knowledge level about the COVID-19 vaccine among the residents of KSA. To find out the various concerns (beliefs) about COVID-19 and its vaccine among the residents of KSA. To estimate the vaccine acceptance and understand the barriers to accepting the COVID-19 vaccine among residents of KSA. MATERIALS AND METHODS: A web-based, cross-sectional study was conducted from April to June 2021 in a restricted environment on the adult (>18 years) residents of Saudi Arabia. The minimum calculated sample was 685; 796 study samples were finally studied to minimize the sampling error. Snowball sampling was used to select the study samples, after meeting the inclusion criteria. RESULTS: A total of 796 people responded. Only 782 (98.2%) were finally considered after excluding the incomplete information forms. The selected participant's age ranges from 18 years to 80 years. Almost 723 (92%) of the study group knew COVID vaccines. Most of the participants, 370 (47%), preferred USA-manufactured vaccine followed by Saudi Arabia 217 (28%). A total of 259 (33.1%) participants were hesitant to receive the vaccine. Out of 782, half of the participants, 386 (50%), believed the COVID vaccine will prevent the infection. CONCLUSION: The government must implement appropriate culturally accepted interventional vaccination educational campaigns to remove the beliefs, worries regarding the safety and efficacy of COVID-19 vaccines, to increase vaccine acceptance rates.

COVID-19 and SARS-CoV-2 Variants: Current Challenges and Health Concern.

The ongoing coronavirus disease 2019 (COVID-19) outbreak in Wuhan, China, was triggered and unfolded quickly throughout the globe by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The new virus, transmitted primarily through inhalation or contact with infected droplets, seems very contagious and pathogenic, with an incubation period varying from 2 to 14 days. The epidemic is an ongoing public health problem that challenges the present global health system. A worldwide social and economic stress has been observed. The transitional source of origin and its transport to humans is unknown, but speedy human transportation has been accepted extensively. The typical clinical symptoms of COVID-19 are almost like colds. With case fatality rates varying from 2 to 3 percent, a small number of patients may experience serious health problems or even die. To date, there is a limited number of antiviral agents or vaccines for the treatment of COVID-19. The occurrence and pathogenicity of COVID-19 infection are outlined and comparatively analyzed, given the outbreak's urgency. The recent developments in diagnostics, treatment, and marketed vaccine are discussed to deal with this viral outbreak. Now the scientist is concerned about the appearance of several variants over the globe and the efficacy of the vaccine against these variants. There is a need for consistent monitoring of the virus epidemiology and surveillance of the ongoing variant and related disease severity.