Fish ACE2 is not susceptible to SARS-CoV-2

The ongoing pandemic of coronavirus disease 2019 (COVID-19) has reshaped our daily life and caused > 4 million deaths worldwide (https://covid19.who.int/). Although lockdown and vaccination have improved the situation in many countries, imported cases and sporadic outbreaks pose a constant stress to the prevention and control of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent responsible for COVID-19, has a positive-sense single-stranded RNA genome of 30 kb (Coronaviridae Study Group of the International Committee on Taxonomy of Viruses, 2020). We and other groups have demonstrated that the SARS-CoV-2 could use the angiotensin-converting enzyme 2 (ACE2) as cell receptor, including orthologs of a broad range of animal species such as human, bats, ferrets, pigs, cats, and dogs (Hoffmann et al., 2020; Zhou et al., 2020; Liu et al., 2021). Although the evolutionary origin of SARS-CoV-2 can be linked to the discoveries of diverse coronaviruses related to SARS-CoV-2 in wild animals such as bats (Zhou et al., 2020; Wacharapluesadee et al., 2021) and pangolins (Liu et al., 2019; Lam et al., 2020), the direct origin of SARS-CoV-2 in humans remains unknown. In China, several sporadic outbreaks of COVID-19 in 2020 were linked to food in cold chain sold at trade markets, including salmon meat (http://www.nhc.gov.cn/xcs/yqtb/list_gzbd.shtml) (Yang et al., 2020). The detection of SARS-CoV-2 RNA on the surface of frozen meat for as long as 20 days has also been reported (Feng et al., 2021). A concern regarding the potential role of fish in SARS-CoV-2 transmission has also been raised. Therefore, we investigated the susceptibility of fish ACE2 to SARS-CoV-2.     

Molecular deconvolution of the neutralizing antibodies induced by an inactivated SARS-CoV-2 virus vaccine

Dear Editor, The rapid emergence and persistence of the pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has had enormous impacts on global health and the economy.Effective vaccines against SARS-CoV-2 are urgently needed to control the coronavirus disease 2019(COVID-19) pandemic,and multiple vaccines have been found to be efficacious in preventing symptomatic COVID-19(Polack et al.,2020;Wu et al.,2020;Jones and Roy,2021).We have developed a traditional beta-propiolactone-inacti-vated aluminum hydroxide-adjuvanted whole-virion SARS-CoV-2 vaccine (BBIBP-CorV),which elicited protective immune responses in clinical trials (Wang et al.,2020;Xia et al.,2021).The vaccine has been granted conditional approvals or emergency use authorizations (EUAs) in China and other countries.     

Genetic tracing of HCoV-19 for the re-emerging outbreak of COVID-19 in Beijing,China

The ongoing pandemic of coronavirus disease 2019(COVID-19)caused by a novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2,also named as 2019-nCoV or HCoV-19)poses an unprecedented threat to public health(Zhu et al.,2020;Wang et al.,2020;Jiang et al.,2020).The novel HCoV-19 virus has rapidly spread into multiple countries across the world since it was first reported in December 2019.The World Health Organization(WHO)declared COVID-19 as a pandemic on 11th March 2020.As of 4th July,over 10 million confirmed COVID-19 cases have been reported in over 200 countries/regions with more than 0.5 million deaths,including 85,287 documented cases and 4,648 deaths in China(WHO,2020a).     

Repurposing FDA-approved drugs for SARS-CoV-2 through an ELISA-based screening for the inhibition of RBD/ACE2 interaction

Dear Editor, The ongoing coronavirus disease 2019(COVID-19)global pandemic is caused by a novel coronavirus,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which instigates severe and often fatal symptoms.As of September 4th,2020,more than 26 million cases of COVID-19 and almost 900,000 deaths have been reported to WHO.Based on Kissler and colleagues'modeled projections of future viral transmission scenarios,a resurgence in SARS-CoV-2 could occur over the next five years(Kissler et al.,2020).Research and clinical trials are underway to develop vacci-nes and treatments for COVID-19,but there are currently no specific vaccines or treatments for COVID-19(www.who.int),and therapeutic and prophylactic interventions are urgently needed to combat the outbreak of SARS-CoV-2.Of partic-ular importance is the identification of drugs which are effective,less-intrusive,most socioeconomic,and ready-to-use.     

An integrated rapid nucleic acid detection assay based on recombinant polymerase amplification for SARS-CoV-2

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus that causes the outbreak of coronavirus disease 2019 (COVID-19) (Li et al., 2020a). Viral nucleic acid testing is the standard method for the laboratory diagnosis of COVID-19 (Wu et al., 2020a; Zhu et al., 2020). Currently, a variety of qPCR-based detection kits are used for laboratory-based detection and confirmation of SARS-CoV-2 infection (Corman et al., 2020; Hussein et al., 2020; Ruhan et al., 2020; Veyer et al., 2020). Conventional qPCR involves virus inactivation, nucleic acid extraction, and qPCR amplification procedures. Therefore, the process is complicated, which usually takes longer than 2 h, and requires biosafety laboratories and professional staff. Thus, qPCR is not suitable for use in field or medical units. To reduce the operation steps, automatic integrated qPCR detection systems that combine nucleic acid extraction and qPCR amplification in a sealed cartridge were developed to detect viruses in clinical samples (Li et al., 2020b). However, the detection time is still longer than 1 h. Therefore, rapid nucleic acid detection systems are needed to further improve the detection efficiency.     

Re-detectable positive SARS-CoV-2 RNA tests in patients who recovered from COVID-19 with intestinal infection

Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARSCoV-2),a novel coronavirus that causes Coronavirus Disease 2019(COVID-19)(Yang and Wang,2020),has spread to more than 200 countries and infected more than 9,000,000 people as of Jun 2020.Tens of thousands of patients with COVID-19 have recovered and been discharged from hospital.However,there are reports of recovered patients who subsequently tested positive for SARSCoV-2 after discharge(re-detectable positive,RP)(An et al.,2020;Lan et al.,2020),and this has led to increasing focus on the mechanism(s)underlying RP.     

Footprints of SARS-CoV-2 genome diversity in Pakistan, 2020–2021

The rapid spread of SARS-CoV-2 has significantly impacted the worldwide health system. The SARS-CoV-2 currently bears a remarkably low genetic diversity even though it carries one of the largest RNA genomes among viruses (Rausch et al., 2020). However, the coronaviruses harbor the capability of undergoing recombination at a high rate which can lead to the emergence of novel viral derivatives (Rausch et al., 2020; Gribble et al., 2021). This in turn requires not only global surveillance of SARS-CoV-2 genome in various countries but also careful scrutiny in animal genomic reservoirs. Conventionally, RNA viruses evolve with a high mutation rate, however, the presence of ExoN ribonuclease in SARS-CoV-2 genome has made its case different from other viral species (Gribble et al., 2021). The variables of natural selection which potentially drift the SARS-CoV-2 evolutionary dynamics can be recorded by analyzing deposited sequence genomes for its fitness, transmissibility potential, and pathogenicity (Rouchka et al., 2020). This can potentially provide a way to draw a holistic picture at a national level, while simultaneously providing a comparative overview with worldwide sequences.     

Pan-coronavirus fusion inhibitors as the hope for today and tomorrow

The last two decades of the 21st century have seen emerging zoonotic coronavirus(CoV)diseases,including severe acute respiratory syndrome(SARS)(Holmes 2003),Middle East respiratory syndrome(MERS)(Graham et al.,2013)and coronavirus disease 2019(COVID-19)(Jiang et al.,2020).     

Different Laboratory Abnormalities in COVID-19 Patients with Hypertension or Diabetes

We reported recently that hypertension is a risk factor for severe cases of COVID-19, independent of age and other variables (Liu et al. 2020a). An important question is why patients with hypertension and diabetes yield poorer clinical outcomes than those without. Human pathogenic coronavirus SARS-CoV-2 utilizes angiotensin-converting enzyme 2 (ACE2) as a receptor for viral cell entry. Since the levels of ACE2 are substantially increased in patients with hypertension or diabetes, who are treated with ACE inhibitors (ACEIs) and angiotensin Ⅱ type-Ⅰ receptor blockers (ARBs) (Ferrario et al. 2005), Fang and colleagues hypothesized that ACE2-stimulating drugs could potentially increase the risk of developing severe COVID-19 (Fang et al. 2020). This was not supported by a recent study led by Dr. Reynolds (Reynolds et al. 2020), whose analysis showed no positive association for ACEIs or ARBs for either the risk of SARS-CoV-2 infection or severe illness (Reynolds et al. 2020). What else might explain the poorer clinical outcomes of COVID-19 patients with hypertension or diabetes?To explore this question, we re-analysed the same cohort of 99 COVID-19 patients discharged from the general wards of Renmin Hospital of Wuhan University between 5 February 2020 and 14 March 2020 (Ethics approval No: WDRY2020-K124) (Liu et al. 2020a, b).     

Epidemiological,Clinical and Serological Characteristics of Children with Coronavirus Disease 2019 in Wuhan: A Single-centered,Retrospective Study

In December 2019, SARS-CoV-2 was first detected in the samples obtained from three adult patients who suffered from an unknown viral pneumonia in Wuhan (Li et al. 2020). This unknown viral pneumonia is further named as coronavirus disease 2019 (COVID-19) by the World Health Organization. To date, the number of new COVID-19 cases has continued to skyrocket and the impact of SARS-CoV-2 on humans is far greater than any pathogen of this century in both breadth and depth. Previous studies have shown that adults with COVID-19 have symptoms of fever, dry cough, dyspnea, fatigue and lymphocytopenia. Moreover, COVID-19 is more likely to cause death in the elderly, especially those with chronic comorbidities (Huang et al. 2020). In Wuhan, more than 50, 000 COVID-19 cases have been confirmed, including over 780 pediatric patients, and only one child death case (Lu et al. 2020). Although the number of children cases was far fewer than that of adults, COVID-19 might endanger children's health and the information on children remains limited, especially in serological study. In the retrospective study, the investigators analyzed the epidemiological, clinical and serological characteristics of children with COVID-19 in Wuhan in the early stages of the outbreak, which might provide theoretical and practical help in controlling COVID-19 and similar emerging infectious diseases in the future.     

Longitudinal virological changes and underlying pathogenesis in hospitalized COVID-19 patients in Guangzhou,China

Science China Life Sciences - Prolonged viral RNA shedding and recurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in coronavirus disease 2019 (COVID-19) patients have been...     

Structural basis of RNA recognition by the SARS-CoV-2 nucleocapsid phosphoprotein

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19). SARS-CoV-2 is a single-stranded positive-sense RNA virus. Like other coronaviruses, SARS-CoV-2 has an unusually large genome that encodes four structural proteins and sixteen nonstructural proteins. The structural nucleocapsid phosphoprotein N is essential for linking the viral genome to the viral membrane. Both N-terminal RNA binding (N-NTD) and C-terminal dimerization domains are involved in capturing the RNA genome and, the intrinsically disordered region between these domains anchors the ribonucleoprotein complex to the viral membrane. Here, we characterized the structure of the N-NTD and its interaction with RNA using NMR spectroscopy. We observed a positively charged canyon on the surface of the N-NTD that might serve as a putative RNA binding site similarly to other coronaviruses. The subsequent NMR titrations using single-stranded and double-stranded RNA revealed a much more extensive U-shaped RNA-binding cleft lined with regularly distributed arginines and lysines. The NMR data supported by mutational analysis allowed us to construct hybrid atomic models of the N-NTD/RNA complex that provided detailed insight into RNA recognition.     

In silico investigation of ACE2 and the main protease of SARS-CoV-2 with phytochemicals from Myristica fragrans (Houtt.) for the discovery of a novel COVID-19 drug

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), is a new coronavirus strain that was first reported in December 2019 in Wuhan, China. A specific treatment for COVID-19 has yet to be identified. Potential therapeutic targets include SARS-CoV-2 main protease (Mpro) and the SARS-CoV-2 spike-ACE2 interaction. Molecular docking, molecular dynamics (MD), solvent screening for the extraction of the specified compounds, and prediction of the drug properties of certain molecules were the methods used in this study to investigate compounds from the medicinal plant Myristica fragrans, which is one of twelve herbs in Prasachandaeng remedy (PSD). ArgusLab, AutoDock Vina, and AutoDock were used to perform docking tasks. The examined ligands were compared with panduratin A as a standard (Kanjanasirirat et al., 2020), which is a promising medicinal plant molecule for the treatment of COVID-19. Molecular docking revealed that malabaricones B and C and licarins A, B and C bound to SARS-CoV-2/ACE2 and SARS-CoV-2 Mpro with low binding energies compared to that of the standard ligand. Furthermore, appropriate solvent usage is important. Acetone was selected by COSMOquick software for compound extraction in this investigation because it can extract large amounts of all five of the abovementioned M. fragrans compounds. Furthermore, the drug-like properties of these compounds were studied utilizing the Lipinski, Veber, and Ghose criteria. The results revealed that these M. fragrans compounds have potential as effective medicines to combat the COVID-19 pandemic. However, to assess the therapeutic potential of these ligands, additional research is needed, which will use our findings as a foundation.     

IL-15 immunotherapy is a viable strategy for COVID-19

Coronavirus disease 2019 (COVID-19) is a pulmonary inflammatory disease induced by a newly recognized coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection was detected for the first time in the city of Wuhan in China and spread all over the world at the beginning of 2020. Several millions of people have been infected with SARS-CoV-2, and almost 382,867 human deaths worldwide have been reported so far. Notably, there has been no specific, clinically approved vaccine or anti-viral treatment strategy for COVID-19. Herein, we review COVID-19, the viral replication, and its effect on promoting pulmonary fibro-inflammation via immune cell-mediated cytokine storms in humans. Several clinical trials are currently ongoing for anti-viral drugs, vaccines, and neutralizing antibodies against COVID-19. Viral clearance is the result of effective innate and adaptive immune responses. The pivotal role of interleukin (IL)-15 in viral clearance involves maintaining the balance of induced inflammatory cytokines and the homeostatic responses of natural killer and CD8⁺ T cells. This review presents supporting evidence of the impact of IL-15 immunotherapy on COVID-19.     

Asunaprevir,a Potent Hepatitis C Virus Protease Inhibitor,Blocks SARS-CoV-2 Propagation

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has become a global health concern. Various SARS-CoV-2 vaccines have been developed and are being used for vaccination worldwide. However, no therapeutic agents against coronavirus disease 2019 (COVID-19) have been developed so far; therefore, new therapeutic agents are urgently needed. In the present study, we evaluated several hepatitis C virus direct-acting antivirals as potential candidates for drug repurposing against COVID-19. Theses include asunaprevir (a protease inhibitor), daclatasvir (an NS5A inhibitor), and sofosbuvir (an RNA polymerase inhibitor). We found that asunaprevir, but not sofosbuvir and daclatasvir, markedly inhibited SARS-CoV-2-induced cytopathic effects in Vero E6 cells. Both RNA and protein levels of SARS-CoV-2 were significantly decreased by treatment with asunaprevir. Moreover, asunaprevir profoundly decreased virion release from SARS-CoV-2-infected cells. A pseudoparticle entry assay revealed that asunaprevir blocked SARS-CoV-2 infection at the binding step of the viral life cycle. Furthermore, asunaprevir inhibited SARS-CoV-2 propagation in human lung Calu-3 cells. Collectively, we found that asunaprevir displays broad-spectrum antiviral activity and therefore might be worth developing as a new drug repurposing candidate for COVID-19.