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1.
J Clin Virol ; 154: 105244, 2022 09.
Article in English | MEDLINE | ID: covidwho-1991142

ABSTRACT

BACKGROUND: Human adenovirus type B7 (HAdV-B7) has been reported to cause pneumonia. However, there are limited data about the epidemiological and clinical features of HAdV-B7 pneumonia in young adults. METHODS: This retrospective observational study included 52 patients diagnosed of human adenovirus B7 pneumonia in Nanjing, China from February 7, 2016, to February 20, 2016. We retrospectively collected and analyzed clinical, laboratory, and radiologic features, treatments and outcomes. RESULTS: The median age of the 52 patients was 19.5 years (IQR 18.0-21.0). The most common symptoms were fever (50, 96.2%), cough (49, 94.2%), and expectoration (48, 92.3%). Most of the routine hematology and blood chemistry parameters were within the normal range. The predominant abnormal patterns seen on chest CT were unilateral (33, 66%), multifocal (36, 72%), and ground-glass opacity (27, 54%), mainly involving the left lower lobes (41 [36.0%] of 114 affected segments). As the disease progressed in the second week after symptom onset, consolidation and mixed patterns became more common, while the ground glass opacity pattern decreased. The single-agent ribavirin therapy group had a significantly shorter duration of nonrespiratory symptoms, and no statistically significant difference was observed between the single-agent methylprednisolone group and the nonglucocorticoid group. CONCLUSIONS: The main symptoms in immunocompetent patients with adenovirus type 7 are fever, cough and sputum, with no significant abnormalities in laboratory tests. Chest CT scan mostly shows a ground-glass opacity at the beginning of the disease, which subsequently changes to a mixed pattern. Ribavirin and glucocorticoids did not shorten the course of disease.


Subject(s)
Adenoviruses, Human , Coronavirus Infections , Pneumonia, Viral , Pneumonia , Adolescent , Adult , China/epidemiology , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Cough , Disease Outbreaks , Fever/epidemiology , Humans , Lung , Pandemics , Pneumonia/epidemiology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Retrospective Studies , Ribavirin , Treatment Outcome , Young Adult
2.
Cell Chem Biol ; 28(6): 855-865.e9, 2021 06 17.
Article in English | MEDLINE | ID: covidwho-1201399

ABSTRACT

The COVID-19 pandemic has been disastrous to society and effective drugs are urgently needed. The papain-like protease domain (PLpro) of SARS-CoV-2 (SCoV2) is indispensable for viral replication and represents a putative target for pharmacological intervention. In this work, we describe the development of a potent and selective SCoV2 PLpro inhibitor, 19. The inhibitor not only effectively blocks substrate cleavage and immunosuppressive function imparted by PLpro, but also markedly mitigates SCoV2 replication in human cells, with a submicromolar IC50. We further present a convenient and sensitive activity probe, 7, and complementary assays to readily evaluate SCoV2 PLpro inhibitors in vitro or in cells. In addition, we disclose the co-crystal structure of SCoV2 PLpro in complex with a prototype inhibitor, which illuminates their detailed binding mode. Overall, these findings provide promising leads and important tools for drug discovery aiming to target SCoV2 PLpro.


Subject(s)
Coronavirus Papain-Like Proteases/antagonists & inhibitors , Drug Delivery Systems/methods , Drug Development/methods , Protease Inhibitors/administration & dosage , SARS-CoV-2/drug effects , A549 Cells , Animals , Antiviral Agents/administration & dosage , Antiviral Agents/chemistry , Antiviral Agents/metabolism , COVID-19/enzymology , Coronavirus Papain-Like Proteases/chemistry , Coronavirus Papain-Like Proteases/metabolism , Dose-Response Relationship, Drug , HEK293 Cells , HeLa Cells , Humans , Mice , Molecular Docking Simulation/methods , Protease Inhibitors/chemistry , Protease Inhibitors/metabolism , Protein Structure, Secondary , Protein Structure, Tertiary , SARS-CoV-2/chemistry , SARS-CoV-2/enzymology , COVID-19 Drug Treatment
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