Preparation and characterization of immobilized 5-HT1A receptor stationary phase for high throughput screening of the receptor-binding ligands from complex systems like Curcuma wenyujin Y. H. Chen et C. Ling extract.

The incidence of depression has increased significantly during the COVID-19 pandemic. This disease is closely associated with serotonin 1A (5-HT1A) receptor and often treated by complex prescription containing Curcuma wenyujin Y. H. Chen et C. Ling. Therefore, we hypothesized that this herb contains bioactive compounds specially binding to the receptor. However, the rapid discovery of new ligands of 5-HT1A receptor is still challenging due to the lack of efficient screening methods. To address this problem, we developed and characterized a novel approach for the rapid screening of ligands by using immobilized 5-HT1A receptor as the chromatographic stationary phase. Briefly, haloalkane dehalogenase was fused at the C-terminal of 5-HT1A receptor, and the modified 5-HT1A receptor was immobilized on amino-microspheres by the reaction between haloalkane dehalogenase and 6-chlorohexanoic acid linker. Scanning electron microscope and X-ray photo-electron were used to characterize the morphology and element of the immobilized receptor. The binding of three specific ligands to 5-HT1A receptor was investigated by two different methods. Moreover, we examined the feasibility of 5-HT1A receptor colume in high throughput screening of new ligands from complex systems as exemplified by Curcuma wenyujin Y. H. Chen et C. Ling. Gweicurculactone, 2-hydroxy-1-(3,4-dihydroxybenzene)-7-(4'-hydroxybezene)-heptane and curcuminol F were identified as the ligands of 5-HT1A receptor with the binding energies of -7.06 kcal/mol, -7.77 kcal/mol and -5.26 kcal/mol, respectively. Collectively, these results indicated that the immobilized 5-HT1A receptor was capable of screening bioactive compound from complex system, providing an effective methodology for high throughput screening.

Computation of Antigenicity Predicts SARS-CoV-2 Vaccine Breakthrough Variants (preprint)

It has been reported that multiple SARS-CoV-2 variants of concerns (VOCs) including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta) can reduce neutralisation by antibodies, resulting in vaccine breakthrough infections. Virus-antiserum neutralisation assays are typically performed to monitor potential vaccine breakthrough strains. However, such experimental-based methods are slow and cannot instantly validate whether newly emerging variants can break through current vaccines or therapeutic antibodies. To address this, we sought to establish a computational model to predict the antigenicity of SARS-CoV-2 variants by sequence alone and in real time. In this study, we firstly identified the relationship between the antigenic difference transformed from the amino acid sequence and the antigenic distance from the neutralisation titres. Based on this correlation, we obtained a computational model for the receptor binding domain (RBD) of the spike protein to predict the fold decrease in virus-antiserum neutralisation titres with high accuracy (~0.79). Our predicted results were comparable with experimental neutralisation titres of variants, including B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), B.1.429 (Epsilon), P.1 (Gamma), B.1.526 (Iota), B.1.617.1 (Kappa), and C.37 (Lambda), as well as SARS-CoV. Here, we firstly predicted the fold of decrease of B.1.1.529 (Omicron) as 17.4-fold less susceptible to neutralisation. We visualised all 1521 SARS-CoV-2 lineages to indicate variants including B.1.621 (Mu), B.1.630, B.1.633, B.1.649, and C.1.2, which can induce vaccine breakthrough infections in addition to reported VOCs B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Our study offers a quick approach to predict the antigenicity of SARS-CoV-2 variants as soon as they emerge. Furthermore, this approach can facilitate future vaccine updates to cover all major variants. An online version can be accessed at http://jdlab.online .

Emerging SARS-CoV-2 variants expand species tropism to rodents (preprint)

Mice are not susceptible to wildtype SARS-CoV-2 infection. Emerging SARS-CoV-2 variants including B.1.1.7, B.1.351, P.1, and P.3 contain mutations in spike, which have been suggested to associate with an increased recognition of mouse ACE2, raising the postulation that they may have evolved to expand species tropism to rodents. Here, we investigated the capacity of B.1.1.7 and other emerging SARS-CoV-2 variants in infecting mouse (Mus musculus) and rats (Rattus norvegicus) under in vitro and in vivo settings. Our results show that B.1.1.7 and P.3, but not B.1 or wildtype SARS-CoV-2, can utilize mouse and rat ACE2 for virus entry in vitro. High infectious virus titers, abundant viral antigen expression, and pathological changes are detected in the nasal turbinate and lung of B.1.1.7-inocluated mice and rats. Together, these results reveal that the current predominant circulating SARS-CoV-2 variant, B.1.1.7, has gained the capability to expand species tropism to rodents.

Mapping the Immunodominance Landscape of SARS-CoV-2 Spike Protein for the Design of Vaccines against COVID-19 (preprint)

The ongoing coronavirus disease 2019 (COVID-19) pandemic is a serious threat to global public health, and imposes severe burdens on the entire human society. The severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) can cause severe respiratory illness and death. Currently, there are no specific antiviral drugs that can treat COVID-19. Several vaccines against SARS-CoV-2 are being actively developed by research groups around the world. The surface S (spike) protein and the highly expressed internal N (nucleocapsid) protein of SARS-CoV-2 are widely considered as promising candidates for vaccines. In order to guide the design of an effective vaccine, we need experimental data on these potential epitope candidates. In this study, we mapped the immunodominant (ID) sites of S protein using sera samples collected from recently discharged COVID-19 patients. The SARS-CoV-2 S protein-specific antibody levels in the sera of recovered COVID-19 patients were strongly correlated with the neutralising antibody titres. We used epitope mapping to determine the landscape of ID sites of S protein, which identified nine linearized B cell ID sites. Four out of the nine ID sites were found in the receptor-binding domain (RBD). Further analysis showed that these ID sites are potential high-affinity SARS-CoV-2 antibody binding sites. Peptides containing two out of the nine sites were tested as vaccine candidates against SARS-CoV-2 in a mouse model. We detected epitope-specific antibodies and SARS-CoV-2-neutralising activity in the immunised mice. This study for the first time provides human serological data for the design of vaccines against COVID-19.

Protection management and procedures of nuclear medicine imaging during novel coronavirus (2019-nCov) infection epidemic period / 中华核医学与分子影像杂志

At the end of December 2019, acute respiratory infectious diseases caused by a new type of coronavirus were prevalent in Wuhan and other cities of China. Different from radiology examinations, the protocols of nuclear medical imaging examinations are complicated, in which more workplaces and staff are needed, resulting more complex management of patients and higher protection requirements. Combined with the characteristics of SPECT and PET imaging procedures, this paper puts forward some suggestions on the protective process of imaging examinations for patients with confirmed or suspected novel coronavirus infection. The main purpose is to protect medical staff from virus infection, effectively reduce the risk of virus transmission during the examination process, and ensure the medical quality and safety.

Prediction of potential commercially inhibitors against SARS-CoV-2 by multi-task deep model (preprint)

The outbreak of novel coronavirus pneumonia (COVID-19) caused thousands of deaths worldwide, and the number of total infections is still rising. However, the development of effective vaccine for this novel virus would take a few months. Thus it is urgent to identify some potentially effective old drugs that can be used immediately. Fortunately, some compounds that can inhibit coronavirus in vitro have been reported. In this study, the coronavirus-specific dataset was used to fine-tune our pre-trained multi-task deep model. Next we used the re-trained model to select available commercial drugs against targeted proteins of SARS-CoV-2. The results show that abacavir, a powerful nucleoside analog reverse transcriptase inhibitor used to treat HIV, is predicted to have high binding affinity with several proteins of SARS-CoV-2. Almitrine mesylate and roflumilast which are used for respiratory diseases such as chronic obstructive pulmonary disease are also predicted to have inhibitory effect. Overall, ten drugs are listed as potential inhibitors and the important sites for these binding by our model are exhibited. We hope these results would be useful in the fight against SARS-CoV-2.