Natural Products as Potential Therapeutic Agents for SARS-CoV-2: A Medicinal Chemistry Perspective.

Coronavirus is a single-stranded RNA virus discovered by virologist David Tyrrell in 1960. Till now seven human corona viruses have been identified including HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, SARS-CoV, MERS-CoV and SARS-CoV-2. In the present scenario, the SARS-CoV-2 outbreak causing SARS-CoV-2 pandemic, became the most serious public health emergency of the century worldwide. Natural products have long history and advantages for the drug discovery process. Almost 80% of drugs present in market are evolved from the natural resources. With the outbreak of SARS-CoV-2 pandemic, natural product chemists have made significant efforts for the identification of natural molecules which can be effective against the SARS-CoV-2. In current compilation we have discussed in vitro and in vivo anti-viral potential of natural product-based leads for the treatment of SARS-CoV-2. We have classified these leads in different classes of natural products such as alkaloids, terpenoids, flavonoids, polyphenols, quinones, cannabinoids, steroids, glucosinolates, diarylheptanoids, etc. and discussed the efficacy and mode of action of these natural molecules. The present review will surely opens new direction in future for the development of promising drug candidates particularly from the natural origin against coronaviruses and other viral diseases.

Clinicoradiological profile and outcome of cavernous sinus syndrome with coronavirus disease-2019-associated rhino-orbito-cerebral mucormycosis

Objective: With coronavirus disease 2019 (COVID-19) pandemic across the world, there had been an exponential increase in rhino-orbito-cerebral mucormycosis (ROCM). Extension of infection to cavernous sinus leads to cavernous sinus syndrome (CSS). This study aims to describe incidence, clinicoradiological profile, and outcome of CSS positive along with comparative analysis of CSS negative COVID-19-associated ROCM. Material and Method: This was a prospective and observational study conducted from May 1, 2021, to July 31, 2021. Subjects included ROCM with active or recovered COVID-19 (past 6 weeks) and were categorized and staged. CSS was defined as involvement of two or more of third, fourth, fifth, or sixth cranial nerve with one each direct and indirect qualitative neuroradiological features. Clinicoradiological features of CSS-positive and negative COVID-19-associated ROCM groups were compared. Results: Incidence of CSS with COVID-19-associated ROCM was 28%. Mean age of subjects was 44 ± 15 years with 60% being males and 73% were proven ROCM. Significant differences seen across the CSS-positive and negative groups were ocular, nasal, and cerebral findings including eyelid and periocular discoloration, ptosis, proptosis, ophthalmoplegia, nasal discharge, mucosal inflammation, and fever. Oculomotor, trochlear, and abducens nerves were significantly involved more in CSS-positive group. Significant radiological findings across two groups included indirect features in orbit, nose, and paranasal sinuses along with direct features in cavernous sinus. Surgical intervention was more common in CSS-positive group. Mortality in CSS-positive group at 8–24 weeks was 13 and 27%, respectively. Conclusion: Extension of ROCM to CSS was more common in young males in advanced stages of proven ROCM with concurrent COVID-19. CSS-positive group had significant difference in clinicoradiological features involving orbit, nose, paranasal sinuses, and central nervous system as compared to CSS-negative group. This study highlights the need to develop an objective scoring system considering clinical and radiological features for diagnosis of CSS with COVID-19-associated ROCM.

Precompetitive Consensus Building to Facilitate the Use of Digital Health Technologies to Support Parkinson Disease Drug Development through Regulatory Science.

Innovative tools are urgently needed to accelerate the evaluation and subsequent approval of novel treatments that may slow, halt, or reverse the relentless progression of Parkinson disease (PD). Therapies that intervene early in the disease continuum are a priority for the many candidates in the drug development pipeline. There is a paucity of sensitive and objective, yet clinically interpretable, measures that can capture meaningful aspects of the disease. This poses a major challenge for the development of new therapies and is compounded by the considerable heterogeneity in clinical manifestations across patients and the fluctuating nature of many signs and symptoms of PD. Digital health technologies (DHT), such as smartphone applications, wearable sensors, and digital diaries, have the potential to address many of these gaps by enabling the objective, remote, and frequent measurement of PD signs and symptoms in natural living environments. The current climate of the COVID-19 pandemic creates a heightened sense of urgency for effective implementation of such strategies. In order for these technologies to be adopted in drug development studies, a regulatory-aligned consensus on best practices in implementing appropriate technologies, including the collection, processing, and interpretation of digital sensor data, is required. A growing number of collaborative initiatives are being launched to identify effective ways to advance the use of DHT in PD clinical trials. The Critical Path for Parkinson's Consortium of the Critical Path Institute is highlighted as a case example where stakeholders collectively engaged regulatory agencies on the effective use of DHT in PD clinical trials. Global regulatory agencies, including the US Food and Drug Administration and the European Medicines Agency, are encouraging the efficiencies of data-driven engagements through multistakeholder consortia. To this end, we review how the advancement of DHT can be most effectively achieved by aligning knowledge, expertise, and data sharing in ways that maximize efficiencies.