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1.
Nat Commun ; 13(1): 1444, 2022 03 17.
Article in English | MEDLINE | ID: covidwho-1751716

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to have devastating consequences worldwide. Recently, great efforts have been made to identify SARS-CoV-2 host factors, but the regulatory mechanisms of these host molecules, as well as the virus per se, remain elusive. Here we report a role of RNA G-quadruplex (RG4) in SARS-CoV-2 infection. Combining bioinformatics, biochemical and biophysical assays, we demonstrate the presence of RG4s in both SARS-CoV-2 genome and host factors. The biological and pathological importance of these RG4s is then exemplified by a canonical 3-quartet RG4 within Tmprss2, which can inhibit Tmprss2 translation and prevent SARS-CoV-2 entry. Intriguingly, G-quadruplex (G4)-specific stabilizers attenuate SARS-CoV-2 infection in pseudovirus cell systems and mouse models. Consistently, the protein level of TMPRSS2 is increased in lungs of COVID-19 patients. Our findings reveal a previously unknown mechanism underlying SARS-CoV-2 infection and suggest RG4 as a potential target for COVID-19 prevention and treatment.


Subject(s)
COVID-19 , Virus Internalization , Animals , Humans , Mice , RNA , SARS-CoV-2 , Serine Endopeptidases/genetics
2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-322235

ABSTRACT

The outbreak of recently identified 2019 novel coronavirus (2019-nCOV) infection has become a world-wide health threat. Currently, more information is needed for further understanding the transmission, clinical characteristics, and infection control procedures of 2019-nCOV. Recently, the role of the eye in transmitting 2019-nCOV has been intensively discussed. Previous investigations about other high infectious human COVs, that is, severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), may provide helpful information. In this review, we describe the genomics and morphology of human CoVs, the epidemiology, systemic and ophthalmic manifestations, mechanisms of human CoVs infection, and infection control procedures. The role of the eye in the transmission of SARS-CoV and 2019-nCOV is discussed. Although the conjunctiva is directly exposed to extraocular pathogens, and the mucosa of ocular surface and upper respiratory tract is connected by nasolacrimal duct and share same entry receptors for some respiratory viruses. The eye is rarely involved in human CoVs infection, conjunctivitis is quite rare in patients with SARS-CoV and 2019-nCoV infection, and COV RNA positive rate by RT-PCR test in tears and conjunctival secretions from patients with SARS-CoV and 2019-nCoV infection is also very low, which imply that the eye is neither a preferred organ of human COVs infection, nor is a preferred gateway of entry for human COVs to infect respiratory tract. However, pathogens exposed to the ocular surface might be transported to nasal and nasopharyngeal mucosa by constant tear rinsing through lacrimal duct, and then cause respiratory tract infection. Considering close doctor-patient contact is quite common in ophthalmic practice which are apt to transmit human COVs by droplets and fomites, hand hygiene and personal protection are still highly recommended for health care workers to avoid hospital-related viral transmission during ophthalmic practice.

3.
Viruses ; 14(1)2021 12 29.
Article in English | MEDLINE | ID: covidwho-1628815

ABSTRACT

Outbreaks of influenza, caused by the influenza A virus (IAV), occur almost every year in various regions worldwide, seriously endangering human health. Studies have shown that host non-coding RNA is an important regulator of host-virus interactions in the process of IAV infection. In this paper, we comprehensively analyzed the research progress on host non-coding RNAs with regard to the regulation of IAV replication. According to the regulation mode of host non-coding RNAs, the signal pathways involved, and the specific target genes, we found that a large number of host non-coding RNAs directly targeted the PB1 and PB2 proteins of IAV. Nonstructural protein 1 and other key genes regulate the replication of IAV and indirectly participate in the regulation of the retinoic acid-induced gene I-like receptor signaling pathway, toll-like receptor signaling pathway, Janus kinase signal transducer and activator of transcription signaling pathway, and other major intracellular viral response signaling pathways to regulate the replication of IAV. Based on the above findings, we mapped the regulatory network of host non-coding RNAs in the innate immune response to the influenza virus. These findings will provide a more comprehensive understanding of the function and mechanism of host non-coding RNAs in the cellular anti-virus response as well as clues to the mechanism of cell-virus interactions and the discovery of antiviral drug targets.


Subject(s)
Host-Pathogen Interactions , Influenza A virus/genetics , Influenza, Human/immunology , RNA, Untranslated , Virus Replication , Antiviral Agents/immunology , Cell Cycle , Humans , Immunity, Innate , Influenza, Human/virology , MicroRNAs , RNA, Circular , Signal Transduction
4.
Front Endocrinol (Lausanne) ; 12: 727419, 2021.
Article in English | MEDLINE | ID: covidwho-1444039

ABSTRACT

Background: Blood parameters, such as neutrophil-to-lymphocyte ratio, have been identified as reliable inflammatory markers with diagnostic and predictive value for the coronavirus disease 2019 (COVID-19). However, novel hematological parameters derived from high-density lipoprotein-cholesterol (HDL-C) have rarely been studied as indicators for the risk of poor outcomes in patients with severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection. Here, we aimed to assess the prognostic value of these novel biomarkers in COVID-19 patients and the diabetes subgroup. Methods: We conducted a multicenter retrospective cohort study involving all hospitalized patients with COVID-19 from January to March 2020 in five hospitals in Wuhan, China. Demographics, clinical and laboratory findings, and outcomes were recorded. Neutrophil to HDL-C ratio (NHR), monocyte to HDL-C ratio (MHR), lymphocyte to HDL-C ratio (LHR), and platelet to HDL-C ratio (PHR) were investigated and compared in both the overall population and the subgroup with diabetes. The associations between blood parameters at admission with primary composite end-point events (including mechanical ventilation, admission to the intensive care unit, or death) were analyzed using Cox proportional hazards regression models. Receiver operating characteristic curves were used to compare the utility of different blood parameters. Results: Of 440 patients with COVID-19, 67 (15.2%) were critically ill. On admission, HDL-C concentration was decreased while NHR was high in patients with critical compared with non-critical COVID-19, and were independently associated with poor outcome as continuous variables in the overall population (HR: 0.213, 95% CI 0.090-0.507; HR: 1.066, 95% CI 1.030-1.103, respectively) after adjusting for confounding factors. Additionally, when HDL-C and NHR were examined as categorical variables, the HRs and 95% CIs for tertile 3 vs. tertile 1 were 0.280 (0.128-0.612) and 4.458 (1.817-10.938), respectively. Similar results were observed in the diabetes subgroup. ROC curves showed that the NHR had good performance in predicting worse outcomes. The cutoff point of the NHR was 5.50. However, the data in our present study could not confirm the possible predictive effect of LHR, MHR, and PHR on COVID-19 severity. Conclusion: Lower HDL-C concentrations and higher NHR at admission were observed in patients with critical COVID-19 than in those with noncritical COVID-19, and were significantly associated with a poor prognosis in COVID-19 patients as well as in the diabetes subgroup.


Subject(s)
COVID-19/blood , Cholesterol, HDL/blood , Diabetes Mellitus/blood , Aged , Biomarkers/blood , COVID-19/diagnosis , COVID-19/mortality , China , Diabetes Mellitus/diagnosis , Diabetes Mellitus/mortality , Female , Humans , Kaplan-Meier Estimate , Leukocytes/cytology , Male , Middle Aged , Prognosis , ROC Curve , Retrospective Studies , Severity of Illness Index
5.
Chinese Journal of Information on Traditional Chinese Medicine ; 27(8):1-7, 2020.
Article in Chinese | CAB Abstracts | ID: covidwho-1319774

ABSTRACT

Since December 2019, a number of cases of pneumonia with unexplained reasons have been reported in Wuhan, Hubei Province, and a large number of cases have been infected. National Health Commission of the People's Republic of China has named it novel coronavirus pneumonia (COVID-19). With the strengthening of prevention and control forces, the number of mild patients in mobile cabin hospital has increased and a large number of patients have been cured and discharged from the hospital. The rehabilitation program of integrated traditional Chinese and Western medicine needs to be formulated and implemented urgently. Therefore, according to treatment protocols issued by National Health Commission of the People's Republic of China and relevant institutes, and widely discussion of relevant experts of pulmonary rehabilitation, TCM and nutrition, Respiratory Rehabilitation Program (Draft) of Integrated Traditional Chinese and Western Medicine for COVID-19 was compiled, in order to play a positive role in the follow-up epidemic prevention and control.

6.
Front Public Health ; 8: 155, 2020.
Article in English | MEDLINE | ID: covidwho-854038

ABSTRACT

The outbreak of the current 2019 novel coronavirus (2019-nCoV, now named SARS-CoV-2) infection has become a worldwide health threat. Currently, more information is needed so as to further understand the transmission and clinical characteristics of 2019-nCoV infection and the infection control procedures required. Recently, the role of the eye in transmitting 2019-nCoV has been intensively discussed. Previous investigations of other highly infectious human CoVs, that is, severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), may provide useful information. In this review, we describe the genomics and morphology of human CoVs, the epidemiology, systemic and ophthalmic manifestations, and mechanisms of human CoV infection, and recommendations for infection control procedures. The role of the eye in the transmission of 2019-nCoV is discussed in detail. Although the conjunctiva is directly exposed to extraocular pathogens, and the mucosa of the ocular surface and upper respiratory tract are connected by the nasolacrimal duct and share the same entry receptors for some respiratory viruses, the eye is rarely involved in human CoV infection, conjunctivitis is quite rare in patients with 2019-nCoV infection, and the CoV RNA positive rate by RT-PCR test in tears and conjunctival secretions from patients with 2019-nCoV and SARS-CoV infection is also extremely low. This suggests that the eye is neither a preferred organ of human CoV infection nor a preferred gateway of entry for human CoVs for infecting the respiratory tract. However, pathogens that the ocular surface is exposed to might be transported to nasal and nasopharyngeal mucosa by constant tear rinsing through the lacrimal duct system and then cause respiratory tract infection. Considering that close doctor-patient contact is quite common in ophthalmic practice and is apt to transmit human CoVs by droplets and fomites, strict hand hygiene and proper personal protection are highly recommended for health care workers to avoid hospital-related viral transmission during ophthalmic practice.


Subject(s)
COVID-19/transmission , Eye/virology , SARS-CoV-2 , Tears/virology , China , Conjunctiva/virology , Genomics , Humans , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification
7.
Front Endocrinol (Lausanne) ; 11: 525, 2020.
Article in English | MEDLINE | ID: covidwho-690147

ABSTRACT

Background: Diabetes correlates with poor prognosis in patients with COVID-19, but very few studies have evaluated whether impaired fasting glucose (IFG) is also a risk factor for the poor outcomes of patients with COVID-19. Here we aimed to examine the associations between IFG and diabetes at admission with risks of complications and mortality among patients with COVID-19. Methods: In this multicenter retrospective cohort study, we enrolled 312 hospitalized patients with COVID-19 from 5 hospitals in Wuhan from Jan 1 to Mar 17, 2020. Clinical information, laboratory findings, complications, treatment regimens, and mortality status were collected. The associations between hyperglycemia and diabetes status at admission with primary composite end-point events (including mechanical ventilation, admission to intensive care unit, or death) were analyzed by Cox proportional hazards regression models. Results: The median age of the patients was 57 years (interquartile range 38-66), and 172 (55%) were women. At the time of hospital admission, 84 (27%) had diabetes (and 36 were new-diagnosed), 62 (20%) had IFG, and 166 (53%) had normal fasting glucose (NFG) levels. Compared to patients with NFG, patients with IFG and diabetes developed more primary composite end-point events (9 [5%], 11 [18%], 26 [31%]), including receiving mechanical ventilation (5 [3%], 6 [10%], 21 [25%]), and death (4 [2%], 9 [15%], 20 [24%]). Multivariable Cox regression analyses showed diabetes was associated increased risks of primary composite end-point events (hazard ratio 3.53; 95% confidence interval 1.48-8.40) and mortality (6.25; 1.91-20.45), and IFG was associated with an increased risk of mortality (4.11; 1.15-14.74), after adjusting for age, sex, hospitals and comorbidities. Conclusion: IFG and diabetes at admission were associated with higher risks of adverse outcomes among patients with COVID-19.


Subject(s)
Blood Glucose/metabolism , Coronavirus Infections/mortality , Diabetes Complications/mortality , Diabetes Mellitus/physiopathology , Glucose Intolerance/complications , Hyperglycemia/complications , Pneumonia, Viral/mortality , Adult , Aged , Betacoronavirus/isolation & purification , COVID-19 , China/epidemiology , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Diabetes Complications/epidemiology , Diabetes Complications/virology , Diabetes Mellitus/virology , Fasting , Female , Follow-Up Studies , Glucose Intolerance/virology , Hospital Mortality , Hospitalization , Humans , Hyperglycemia/virology , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Prognosis , Retrospective Studies , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Survival Rate
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