Multiple functions of heterogeneous nuclear ribonucleoproteins in the positive single-stranded RNA virus life cycle.

The heterogeneous nuclear ribonucleoproteins (hnRNPs) are a diverse family of RNA binding proteins that are implicated in RNA metabolism, such as alternative splicing, mRNA stabilization and translational regulation. According to their different cellular localization, hnRNPs display multiple functions. Most hnRNPs were predominantly located in the nucleus, but some of them could redistribute to the cytoplasm during virus infection. HnRNPs consist of different domains and motifs that enable these proteins to recognize predetermined nucleotide sequences. In the virus-host interactions, hnRNPs specifically bind to viral RNA or proteins. And some of the viral protein-hnRNP interactions require the viral RNA or other host factors as the intermediate. Through various mechanisms, hnRNPs could regulate viral translation, viral genome replication, the switch of translation to replication and virion release. This review highlights the common features and the distinguish roles of hnRNPs in the life cycle of positive single-stranded RNA viruses.

Case report on cured COVID-19 patients with viral nucleic acid test positive in fecal specimens in Chongqing, China

The outbreak of the novel coronavirus in China (2019-nCoV) has spread to all 31 provinces in China and more than 24 countries in the world. The cure criterion was based on the negative results with respiratory specimens in real-time reverse transcription polymerise chain reaction (RT-PCR) assays with an interval of 24 hrs. This report describes the controversial viral nucleic acid test in 27 cases after hospitalization for medical treatment for various periods. Of 27 cases, 6 cases showed positive results for fecal specimen, and 2 cases showed negative results with respiratory secretion but positive with fecal specimen. In summary, the consistence of results of nucleic acid test with different type of specimens from patients infected with 2019-nCoV varied, deeper research is needed to reveal the criteria of nucleic acid detection during different stages of the 2019-nCoV infection.

Functions of Viroporins in the Viral Life Cycle and Their Regulation of Host Cell Responses.

Viroporins are virally encoded transmembrane proteins that are essential for viral pathogenicity and can participate in various stages of the viral life cycle, thereby promoting viral proliferation. Viroporins have multifaceted effects on host cell biological functions, including altering cell membrane permeability, triggering inflammasome formation, inducing apoptosis and autophagy, and evading immune responses, thereby ensuring that the virus completes its life cycle. Viroporins are also virulence factors, and their complete or partial deletion often reduces virion release and reduces viral pathogenicity, highlighting the important role of these proteins in the viral life cycle. Thus, viroporins represent a common drug-protein target for inhibiting drugs and the development of antiviral therapies. This article reviews current studies on the functions of viroporins in the viral life cycle and their regulation of host cell responses, with the aim of improving the understanding of this growing family of viral proteins.

Clinical features and death risk factors in COVID-19 patients with cancer: a retrospective study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread around the world. This retrospective study aims to analyze the clinical features of COVID-19 patients with cancer and identify death outcome related risk factors. METHODS: From February 10th to April 15th, 2020, 103 COVID-19 patients with cancer were enrolled. Difference analyses were performed between severe and non-severe patients. A propensity score matching (PSM) analysis was performed, including 103 COVID-19 patients with cancer and 206 matched non-cancer COVID-19 patients. Next, we identified death related risk factors and developed a nomogram for predicting the probability. RESULTS: In 103 COVID-19 patients with cancer, the main cancer categories were breast cancer, lung cancer and bladder cancer. Compared to non-severe patients, severe patients had a higher median age, and a higher proportion of smokers, diabetes, heart disease and dyspnea. In addition, most of the laboratory results between two groups were significantly different. PSM analysis found that the proportion of dyspnea was much higher in COVID-19 patients with cancer. The severity incidence in two groups were similar, while a much higher mortality was found in COVID-19 patients with cancer compared to that in COVID-19 patients without cancer (11.7% vs. 4.4%, P = 0.028). Furthermore, we found that neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) were related to death outcome. And a nomogram based on the factors was developed. CONCLUSION: In COVID-19 patients with cancer, the clinical features and laboratory results between severe group and non-severe group were significantly different. NLR and CRP were the risk factors that could predict death outcome.

Tracing genetic signatures of bat-to-human coronaviruses and early transmission of North American SARS-CoV-2.

Highly pathogenic coronaviruses, including SARS-CoV-2, SARS-CoV and MERS-CoV, are thought to be transmitted from bats to humans, but the viral genetic signatures that contribute to bat-to-human transmission remain largely obscure. In this study, we identified an identical ribosomal frameshift motif among the three bat-human pairs of viruses and strong purifying selection after jumping from bats to humans. This represents genetic signatures of coronaviruses that are related to bat-to-human transmission. To further trace the early human-to-human transmission of SARS-CoV-2 in North America, a geographically stratified genome-wide association study (North American isolates and the remaining isolates) and a retrospective study were conducted. We determined that the single nucleotide polymorphisms (SNPs) 1,059.C > T and 25,563.G > T were significantly associated with approximately half of the North American SARS-CoV-2 isolates that accumulated largely during March 2020. Retrospectively tracing isolates with these two SNPs was used to reconstruct the early, reliable transmission history of North American SARS-CoV-2, and European isolates (February 26, 2020) showed transmission 3 days earlier than North American isolates and 17 days earlier than Asian isolates. Collectively, we identified the genetic signatures of the three pairs of coronaviruses and reconstructed an early transmission history of North American SARS-CoV-2. We envision that these genetic signatures are possibly diagnosable and predic markers for public health surveillance.

Indications for and contraindications of immune checkpoint inhibitors in cancer patients with COVID-19 vaccination.

The COVID-19 pandemic has lasted over 1 year and will not disappear in a short time. There is no specific remedy against the virus as yet. Vaccination is thus far one of the most important strategies for preventing COVID-19. Cancer patients with COVID-19 have a higher mortality because of immunosuppression. Immune checkpoint inhibitors (ICIs) are a novel anticancer strategy for blocking inhibitory pathways, which are related to the immune response. There is a question regarding whether COVID-19 vaccination and ICI treatment impact each other in cancer patients. This review explores both sides of the relationship between ICI treatment and COVID-19 vaccination and suggests good efficacy and safety of ICI treatment after COVID-19 vaccination as well as little impact on the virus protection and toxicity associated with COVID-19 vaccination during ICI treatment.

Lay abstract The COVID-19 pandemic has lasted over 1 year. Vaccination is a promising strategy for preventing COVID-19. Cancer patients are prone to infection with COVID-19, and these patients have high mortality. Immune checkpoint inhibitors (ICIs) are a novel anticancer strategy. Whether COVID-19 vaccination and ICI treatment impact each other in cancer patients remains unknown. This review explores both sides of the relationship between ICI treatment and COVID-19 vaccination and suggests good efficacy and safety of ICI treatment after COVID-19 vaccination as well as little impact on the virus protection and toxicity associated with COVID-19 vaccination during ICI treatment.

Clinical characteristics and a decision tree model to predict death outcome in severe COVID-19 patients.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) spreads rapidly among people and causes a pandemic. It is of great clinical significance to identify COVID-19 patients with high risk of death. METHODS: A total of 2169 adult COVID-19 patients were enrolled from Wuhan, China, from February 10th to April 15th, 2020. Difference analyses of medical records were performed between severe and non-severe groups, as well as between survivors and non-survivors. In addition, we developed a decision tree model to predict death outcome in severe patients. RESULTS: Of the 2169 COVID-19 patients, the median age was 61 years and male patients accounted for 48%. A total of 646 patients were diagnosed as severe illness, and 75 patients died. An older median age and a higher proportion of male patients were found in severe group or non-survivors compared to their counterparts. Significant differences in clinical characteristics and laboratory examinations were found between severe and non-severe groups, as well as between survivors and non-survivors. A decision tree, including three biomarkers, neutrophil-to-lymphocyte ratio, C-reactive protein and lactic dehydrogenase, was developed to predict death outcome in severe patients. This model performed well both in training and test datasets. The accuracy of this model were 0.98 in both datasets. CONCLUSION: We performed a comprehensive analysis of COVID-19 patients from the outbreak in Wuhan, China, and proposed a simple and clinically operable decision tree to help clinicians rapidly identify COVID-19 patients at high risk of death, to whom priority treatment and intensive care should be given.

Several FDA-approved drugs effectively inhibit SARS-CoV-2 infection in vitro (preprint)

To identify drugs that are potentially used for the treatment of COVID-19, the potency of 1403 FDA-approved drugs were evaluated using a robust pseudovirus assay and the candidates were further confirmed by authentic SARS-CoV-2 assay. Four compounds, Clomiphene (citrate), Vortioxetine, Vortioxetine (hydrobromide) and Asenapine (hydrochloride), showed potent inhibitory effects in both pseudovirus and authentic virus assay. The combination of Clomiphene (citrate), Vortioxetine and Asenapine (hydrochloride) is much more potent than used alone, with IC50 of 0.34 M.