ABSTRACT
INTRODUCTION: The size and complexity of virtual screening libraries in drug discovery have skyrocketed in recent years, reaching up to multiple billions of accessible compounds. However, virtual screening of such ultra-large libraries poses several challenges associated with preparing the libraries, sampling, and pre-selection of suitable compounds. The utilization of artificial intelligence (AI)-assisted screening approaches, such as deep learning, poses a promising countermeasure to deal with this rapidly expanding chemical space. For example, various AI-driven methods were recently successfully used to identify novel small molecule inhibitors of the SARS-CoV-2 main protease (Mpro). AREAS COVERED: This review focuses on presenting various kinds of virtual screening methods suitable for dealing with ultra-large libraries. Challenges associated with these computational methodologies are discussed, and recent advances are highlighted in the example of the discovery of novel Mpro inhibitors targeting the SARS-CoV-2 virus. EXPERT OPINION: With the rapid expansion of the virtual chemical space, the methodologies for docking and screening such quantities of molecules need to keep pace. Employment of AI-driven screening compounds has already been shown to be effective in a range from a few thousand to multiple billion compounds, furthered by de novo generation of drug-like molecules without human interference.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Artificial Intelligence , Molecular Docking Simulation , Drug Discovery/methods , Protease Inhibitors/pharmacology , Antiviral Agents/pharmacology , Antiviral Agents/chemistrySubject(s)
Abdominal Pain/diagnostic imaging , ChAdOx1 nCoV-19/adverse effects , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnostic imaging , Venous Thrombosis/chemically induced , Venous Thrombosis/diagnostic imaging , Abdominal Pain/chemically induced , Adult , Endoscopy, Digestive System , Female , Humans , Portal System , Thrombocytopenia/therapy , Venous Thrombosis/therapyABSTRACT
The pathogenesis of autoimmune complications triggered by SARS-CoV2 has not been completely elucidated. Here, we performed an analysis of the cellular immune status, cell ratios, and monocyte populations of patients with COVID-19 treated in the intensive care unit (ICU) (cohort 1, N = 23) and normal care unit (NCU) (cohort 2, n = 10) compared with control groups: patients treated in ICU for noninfectious reasons (cohort 3, n = 30) and patients treated in NCU for infections other than COVID-19 (cohort 4, n = 21). Patients in cohort 1 presented significant differences in comparison with the other cohorts, including reduced frequencies of lymphocytes, reduced CD8+T-cell count, reduced percentage of activated and intermediate monocytes and an increased B/T8 cell ratio. Over time, patients in cohort 1 who died presented with lower counts of B, T, CD4+ T, CD8+ T-lymphocytes, NK cells, and activated monocytes. The B/T8 ratio was significantly lower in the group of survivors. In cohort 1, significantly higher levels of IgG1 and IgG3 were found, whereas cohort 3 presented higher levels of IgG3 compared to controls. Among many immune changes, an elevated B/T8-cell ratio and a reduced rate of activated monocytes were mainly observed in patients with severe COVID-19. Both parameters were associated with death in cohort 1.
Subject(s)
B-Lymphocytes/immunology , COVID-19/immunology , Monocytes/immunology , SARS-CoV-2/immunology , Aged , Antibodies, Viral/immunology , B-Lymphocytes/pathology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/pathology , COVID-19/pathology , Female , Humans , Immunoglobulin G/immunology , Lymphocyte Count , Male , Middle Aged , Monocytes/pathology , Prospective Studies , Severity of Illness IndexABSTRACT
During submission the author name Andreas Link was unfortunately omitted. The correct author list reads as follows.