Pandemic strategies with computational and structural biology against COVID-19: A retrospective.

The emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which is the etiologic agent of the coronavirus disease 2019 (COVID-19) pandemic, has dominated all aspects of life since of 2020. Research studies on the virus and exploration of therapeutic and preventive strategies has been moving at rapid rates to control the pandemic. In the field of bioinformatics or computational and structural biology, recent research strategies have used multiple disciplines to compile large datasets to uncover statistical correlations and significance, visualize and model proteins, perform molecular dynamics simulations, and employ the help of artificial intelligence and machine learning to harness computational processing power to further the research on COVID-19, including drug screening, drug design, vaccine development, prognosis prediction, and outbreak prediction. These recent developments should help us better understand the viral disease and develop the much-needed therapies and strategies for the management of COVID-19.

MutScape: an analytical toolkit for probing the mutational landscape in cancer genomics.

Cancer genomics has been evolving rapidly, fueled by the emergence of numerous studies and public databases through next-generation sequencing technologies. However, the downstream programs used to preprocess and analyze data on somatic mutations are scattered in different tools, most of which require specific input formats. Here, we developed a user-friendly Python toolkit, MutScape, which provides a comprehensive pipeline of filtering, combination, transformation, analysis and visualization for researchers, to easily explore the cohort-based mutational characterization for studying cancer genomics when obtaining somatic mutation data. MutScape not only can preprocess millions of mutation records in a few minutes, but also offers various analyses simultaneously, including driver gene detection, mutational signature, large-scale alteration identification and actionable biomarker annotation. Furthermore, MutScape supports somatic variant data in both variant call format and mutation annotation format, and leverages caller combination strategies to quickly eliminate false positives. With only two simple commands, robust results and publication-quality images are generated automatically. Herein, we demonstrate the ability of MutScape to correctly reproduce known results using breast cancer samples from The Cancer Genome Atlas. More significantly, discovery of novel results in cancer genomic studies is enabled through the advanced features in MutScape. MutScape is freely available on GitHub, at https://github.com/anitalu724/MutScape.

Responses to crizotinib and cabozantinib in patient with lung adenocarcinoma harboring mesenchymal-epithelial transition factor exon 14 skipping mutation: A case report.

RATIONALE: Lung cancer is a leading cause of cancer-related mortality worldwide. Currently, targeted therapy has proved highly efficient in the treatment of advanced non-small cell lung cancer (NSCLC). Mesenchymal-epithelial transition factor (MET) is considered a validated molecular target in NSCLC. Given the low incidence of MET exon 14 skipping mutation, the planning of precision treatment for patients is a clinical problem that needs to be solved. In this report, we present a MET-positive case that benefited from crizotinib and cabozantinib treatment. PATIENT CONCERNS: A 77-year-old patient was diagnosed with lung adenocarcinoma in our hospital. Positron emission tomography-computed tomography (PET-CT) showed a right upper lobe mass (58 × 56 mm, SUVmax 15.6), right hilar enlarged lymph nodes, and multiple bone and left adrenal metastases (c-T3N1M1c). DIAGNOSES: MET exon 14 mutation (exon14, c.2888-1G>C) was examined using the lung puncture sample by next generation sequencing. Therefore, the patient was diagnosed with late-stage lung adenocarcinoma with MET exon14 skipping gene mutation. INTERVENTIONS: Crizotinib was given as the first-line treatment from August 2019. Considering the resistance of crizotinib, cabozantinib was given for second-line treatment. OUTCOMES: Crizotinib was administered (250 mg bid) for 8 months, and her disease achieved partial regression (PR) and progression-free survival (PFS), which lasted for 8 months. The patient also reached PR after the second-line treatment with cabozantinib, and is currently under follow-up, with an overall survival (OS) of >12 months. LESSONS: As MET exon 14 skipping mutation is rare in clinical practices, MET-TKIs (tyrosine kinase inhibitors) treatment can boost curative effects and improve prognosis of patients with advanced lung adenocarcinoma. This case report supports a rationale for the treatment of lung adenocarcinoma patients with a MET exon 14 skipping mutation and provides alternative treatment options for these types of NSCLC patients.

Update on Antiviral Strategies Against COVID-19: Unmet Needs and Prospects.

By December 2020, the COVID-19 pandemic had caused more than 74 million confirmed cases and 1.6 million related deaths around the world. However, only a few drugs have been approved in certain areas and for use in conditional patients, and the vaccine candidates were only recently approved or authorized for emergency use without being fully implemented worldwide, suggesting that we are yet to reach effective control of the current outbreak as its uninhibited transmission continues precariously. Over the past few months, several therapeutic candidates have been proven ineffective in large clinical trials, while some other agents exhibited promising preliminary results. Meanwhile, the investigation of SARS-CoV-2-specific antivirals is underway. Despite still being preclinical, these agents could be beneficial for the long-term control of COVID-19 and deserve more research focus. In this article, we update the current status of therapeutic candidates that have been examined for COVID-19 management, including the virus-targeting inhibitors and host-targeting agents, with their antiviral efficacy in vitro, in vivo, and in clinical studies. Finally, we highlight the current challenges and future prospect of developing potent therapeutic agents against COVID-19.