Recent advances in small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase / 药学学报

Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

Efficacy and prognostic analysis of orthopedic surgery in patients with newly diagnosed multiple myeloma / 中华内科杂志

Objective: To evaluate the efficacy and prognosis of orthopedic surgical resection surgery in patients with newly diagnosed multiple myeloma (NDMM). Methods: This retrospective cohort study collected clinical data of patients with NDMM who underwent surgery due to spinal cord compression or pathological long-bone fractures at the Peking Union Medical College Hospital from 1 January 2003 to 31 December 2021. Patients who received biopsy or vertebroplasty/kyphoplasty were excluded and patients with the same degree of bone disease and who did not undergo any surgical intervention were selected as controls. Visual analogue scale (VAS) and physical status (ECOG) scores, progression-free survival (PFS), and overall survival (OS) were compared. Statistical analysis included the χ2-test, t-test, and Kaplan-Meier methods. Results: Baseline data were compared between the surgical group (n=40 with 43 interventions) and the non-surgical group (n=80), and included sex, age, paraprotein type, International Staging System (ISS), number of lytic lesions, cytogenetic abnormalities, first-line treatment, and the proportion of patients receiving autologous stem cell transplantation (ASCT) (all P>0.05). Serum M protein levels in the surgical group were significantly lower than those of the non-surgical group [(21.95±16.44) g/L vs. (36.18±20.85) g/L, P=0.005]. The surgical lesions involved the axial skeleton (79.1%, 34/43) or the extremities (20.9%, 9/43). VAS and ECOG scores improved significantly after surgery (VAS: 2.30±0.80 vs. 6.60±1.50, P<0.001; ECOG: 2.09±0.59 vs. 3.09±0.73, P<0.001). The median follow-up time was 51 months. Kaplan-Meier survival analysis suggested that the median PFS (25 vs. 29 months) and OS (46 vs. 60 months) were comparable between the surgical and non-surgical intervention groups (both P>0.05). Subgroup analysis showed that among patients with ISS Ⅰ or those who had received ASCT, PFS in the surgical group was similar to that of the non-surgical intervention group (both P>0.05), while OS was worse (P=0.005, 0.017). Patients with ISS Ⅱ/Ⅲ scores or without ASCT had similar PFS and OS between the surgical and non-surgical intervention groups (all P>0.05). Cox multivariate analysis suggested that ISS and ASCT were independent prognostic factors for OS (ISS: HR=0.42, 95%CI 0.19-0.93, P=0.031; ASCT: HR=0.41, 95%CI 0.18-0.97, P=0.041), while orthopedic surgery did not influence survival (P=0.233). Conclusion: For patients with NDMM, orthopedic surgical resection decreased bone-related complications and improved quality of life, but did not affect survival.

Advances in the research of HIV-1 envelope glycoprotein gp120 inhibitors / 药学学报

From the process of human immunodeficiency virus-1 (HIV-1) invading cells, the combination of gp120 and CD4 is the first step for HIV-1 to invade cells. Interfering with this process can prevent HIV from recognizing target cells and inhibit virus replication. Therefore, HIV-1 gp120 is an important part of the HIV-1 life cycle. Fostesavir, a phosphatate prodrug derived from the gp120 inhibitor BMS-626529 modified by the prodrug strategy, was approved for the treatment of adult patients with multidrug resistant HIV-1 infection by the US FDA and the European Medicines Agency in 2020 and 2021, respectively. In this review, we focus on the research progress of small molecule inhibitors targeting the interaction of gp120-CD4 from the perspective of medicinal chemistry, in order to provide reference for the subsequent research of gp120 inhibitors.

Application of four intraocular lens calculation formulas in patients with super-high myopia complicated with cataract / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the accuracy of SRK/T, Haigis, Barrett Universal II and Wang-Koch modified SRK/T formula in the operation of cataract complicated by super-high myopia.METHODS: A total of 44 cases(52 eyes)with super-high myopia complicated with cataract who underwent phacoemulsification with tension ring implantation combined with intraocular lens implantation in our hospital from January 2020 to June 2021 were collected. SRK/T, Haigis, Barrett Universal Ⅱ formula and Wang-Koch modified SRK/T formula were used to calculate the postoperative reserved diopter before surgery, and the actual diopter was measured by comprehensive optometry at 3mo after surgery. The mean absolute refractive error(MAE)of four formulas was obtained to evaluate the accuracy of the calculation formula.RESULTS: The MAE of SRK/T formula, Haigis formula, Barrett Universal Ⅱ formula and Wang-Koch modified SRK/T formula were 0.86(0.56, 1.20), 0.79(0.56, 1.16), 0.68(0.30, 0.87), 0.65(0.43, 0.75)D, respectively, and MAE of SRK/T formula and Haigis formula were significantly higher than those of Barrett Universal Ⅱ formula and Wang-Koch modified SRK/T formula(P<0.01). According to preoperative corneal curvature(K), enrolled patients were divided into K >46D group(12 eyes), 44D< K ≤46D group(24 eyes), and K ≤44D group(16 eyes). The MAE of SRK/T formula and Haigis formula were significantly higher than those of Barrett Universal Ⅱ formula and Wang-Koch modified SRK/T formula in the three groups(P<0.01). According to preoperative axial length(AL), patients were divided into AL ≤30 mm group(24 eyes)and AL >30mm group(28 eyes). The MAE of SRK/T formula and Haigis formula in two groups were significantly higher than those of Barrett Universal Ⅱ formula and Wang-Koch modified SRK/T formula(P<0.05).CONCLUSIONS: Wang-Koch modified SRK/T formula and Barrett Universal Ⅱ formula are more accurate in predicting the degree of intraocular lens in patients with super-high myopia complicated with cataract.

Effect of multimodal mirror therapy on upper limb and hand function for stroke patients / 中国康复理论与实践

ObjectiveTo investigate the effect of multimodal mirror therapy on upper limb and hand function in stroke patients. MethodsFrom April, 2021 to August, 2022, 60 stroke patients from the Department of Rehabilitation Medicine of Zhejiang Provincial People's Hospital were randomly divided into group A (n = 20), group B (n = 20) and group C (n = 20). All the patients accepted routine rehabilitation, while group B accepted mirror therapy, and group C accepted multimodal mirror therapy, in addition, for six weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), Upper Extremity Function Test (UEFT) and modified Barthel Index (MBI), while the maximum grip strength and pinch strength of the affected hand were measured. ResultsThe FMA-UE score, UEFT score, maximum hand grip strength and pinch strength, and MBI scores improved in all groups after treatment (|t| > 7.878, P < 0.001), and it was the most in group C (F > 12.563, P < 0.001). ConclusionMultimodal mirror therapy may further improve the upper limb motor function and hand function of stroke patients, as well as the strength of the affected hand and the activities of daily living.

Association Between Constipation and a Reduction in Lower Limb Muscle Strength in Preoperative Patients with Thoracic Spinal Tumors / 中国医学科学杂志(英文版)

Objective To investigate the clinical symptoms experienced by patients with thoracic spinal tumors and verify the associated symptoms that are predictive of a decline in muscle strength in the lower limbs. Methods A single-center, retrospective cross-sectional study was conducted on in-patients diagnosed with epidural thoracic spinal tumors between January 2011 and May 2021. The study involved a review of electronic medical records and radiographs and the collection of clinical data. The differences in clinical manifestations between patients with constipation and those without constipation were analyzed. Binary logistic regression analyses were performed to identify risk factors associated with a decline in muscle strength in the lower limbs.Results A total of 227 patients were enrolled, including 131 patients with constipation and 96 without constipation. The constipation group had a significantly higher proportion of patients who experienced difficulty walking or paralysis compared to those without constipation prior to surgery (83.2% vs. 17.7%, χ2 = 99.035,P < 0.001). Constipation (OR = 9.522, 95%CI: 4.150-21.849, P < 0.001) and urinary retention (OR = 14.490, 95%CI: 4.543-46.213, P < 0.001) were independent risk factors for muscle strength decline in the lower limbs. Conclusions The study observed that patients with thoracic spinal tumors who experienced constipation symptoms had a higher incidence of lower limb weakness. Moreover, the analysis revealed that constipation and urinary retention were independent risk factors associated with a preoperative decline in muscle strength of lower limbs.

Analysis on the status quo of the awareness rate of core knowledge of cancer prevention and treatment and its influencing factors among residents in Liaoning Province in 2021 / 中华预防医学杂志

Objective: To analyze the status quo of the knowledge and related factors of cancer prevention and treatment among residents in Liaoning Province in 2021. Methods: From August to November 2021, through network sampling method, 17 474 permanent residents aged 15-69 years in Liaoning Province were surveyed. The WeChat public account was used to collect information such as demographic characteristics and core knowledge of cancer prevention and treatment. The Chi-square test was used to compare the difference of the level of the cancer prevention and treatment knowledge among different groups. The multivariate logistic regression model was used to analyze the related factors. Results: Among the 17 474 subjects, 43.1% (7 528) were male and 58.7% (10 262) were urban residents. The overall awareness rate was 72.3%, and the awareness rate of cancer cognition, prevention, early diagnosis and treatment, cancer management and rehabilitation were 71.4%, 67.6%, 72.7%, 83.4% and 63.5%, respectively. The multivariate logistic regression model showed that the residents who were man (OR: 0.850, 95%CI: 0.781-0.925), in rural areas (OR: 0.753, 95%CI: 0.694-0.817), 55-59 years old (OR: 0.851, 95%CI: 0.751-0.963), quitters (OR: 0.721, 95%CI: 0.640-0.813) and smoker (OR: 0.724, 95%CI: 0.654-0.801) had lower awareness rates, while the residents who were 35-54 years old (OR: 1.312, 95%CI: 1.202-1.432), with an educational level of junior high school/senior high school/college degree or above (OR: 1.834-5.130, 95%CI: 1.575-6.047), technical personnel (OR: 1.592, 95%CI: 1.367-1.854), civil servant/institution staff (OR: 1.282, 95%CI: 1.094-1.503), enterprise/business/service staff (OR: 1.218, 95%CI: 1.071-1.385), retired (OR: 1.324, 95%CI: 1.114-1.573) and with family history of cancer (OR: 1.369, 95%CI: 1.266-1.481) had higher awareness rates. Conclusion: The level of the awareness of core knowledge of cancer prevention and treatment among residents in Liaoning Province has met the requirements of the Healthy China Action. Region, gender, education level, age, family history of cancer and smoking are relevant factors.

Analysis of risk factors for depth of invasion and angiolymphatic invasion for circumferential superficial esophageal squamous cell carcinoma and precancerous lesion / 中华肿瘤杂志

Objective: To analyze clinicopathological features of circumferential superficial esophageal squamous cell carcinoma and precancerous lesions and investigate the risk factors for deep submucosal invasion and angiolymphatic invasion retrospectively. Methods: A total of 116 cases of esophageal squamous epithelial high-grade intraepithelial neoplasia or squamous cell carcinoma diagnosed by gastroscopy, biopsy pathology and endoscopic resection pathology during November 2013 to October 2021 were collected, and their clinicopathological features were analyzed. The independent risk factors of deep submucosal invasion and angiolymphatic invasion were analyzed by logistic regression model. Results: The multivariate logistic regression analysis showed that drinking history (OR=3.090, 95% CI: 1.165-8.200; P<0.05), The AB type of intrapapillary capillary loop (IPCL) (OR=11.215, 95% CI: 3.955-31.797; P<0.05) were the independent risk factors for the depth of invasion. The smoking history (OR=5.824, 95% CI: 1.704-19.899; P<0.05), the presence of avascular area (AVA) (OR=3.393, 95% CI: 1.285-12.072; P<0.05) were the independent factors for the angiolymphatic invasion. Conclusions: The risk of deep submucosal infiltration is greater for circumferential superficial esophageal squamous cell carcinoma patients with drinking history and IPCL type B2-B3 observed by magnifying endoscopy, while the risk of angiolymphatic invasion should be vigilant for circumferential superficial esophageal squamous cell carcinoma patients with smoking history and the presence of AVA observed by magnifying endoscopy. Ultrasound endoscopy combined with narrowband imagingand magnification endoscopy can improve the accuracy of preoperative assessment of the depth of infiltration of superficial squamous cell carcinoma and precancerous lesions and angiolymphaticinvasion in the whole perimeter of the esophagus, and help endoscopists to reasonably grasp the indications for endoscopic treatment.

Risk factors analysis and prediction model construction of submucosal deep infiltration of early colorectal tumor / 中华肿瘤杂志

Objective: To investigate the risk factors for the development of deep infiltration in early colorectal tumors (ECT) and to construct a prediction model to predict the development of deep infiltration in patients with ECT. Methods: The clinicopathological data of ECT patients who underwent endoscopic treatment or surgical treatment at the Cancer Hospital, Chinese Academy of Medical Sciences from August 2010 to December 2020 were retrospectively analyzed. The independent risk factors were analyzed by multifactorial regression analysis, and the prediction models were constructed and validated by nomogram. Results: Among the 717 ECT patients, 590 patients were divided in the within superficial infiltration 1 (SM1) group (infiltration depth within SM1) and 127 patients in the exceeding SM1 group (infiltration depth more than SM1). There were no statistically significant differences in gender, age, and lesion location between the two groups (P>0.05). The statistically significant differences were observed in tumor morphological staging, preoperative endoscopic assessment performance, vascular tumor emboli and nerve infiltration, and degree of tumor differentiation (P<0.05). Multivariate regression analysis showed that only erosion or rupture (OR=4.028, 95% CI: 1.468, 11.050, P=0.007), localized depression (OR=3.105, 95% CI: 1.584, 6.088, P=0.001), infiltrative JNET staging (OR=5.622, 95% CI: 3.029, 10.434, P<0.001), and infiltrative Pit pattern (OR=2.722, 95% CI: 1.347, 5.702, P=0.006) were independent risk factors for the development of deep submucosal infiltration in ECT. Nomogram was constructed with the included independent risk factors, and the nomogram was well distinguished and calibrated in predicting the occurrence of deep submucosal infiltration in ECT, with a C-index and area under the curve of 0.920 (95% CI: 0.811, 0.929). Conclusion: The nomogram prediction model constructed based on only erosion or rupture, local depression, infiltrative JNET typing, and infiltrative Pit pattern has a good predictive efficacy in the occurrence of deep submucosal infiltration in ECT.

Risk factors for residual cancer or lymph node metastasis after endoscopic noncurable resection of early colorectal cancer / 中华肿瘤杂志

Objective: Risk factors related to residual cancer or lymph node metastasis after endoscopic non-curative resection of early colorectal cancer were analyzed to predict the risk of residual cancer or lymph node metastasis, optimize the indications of radical surgical surgery, and avoid excessive additional surgical operations. Methods: Clinical data of 81 patients who received endoscopic treatment for early colorectal cancer in the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences from 2009 to 2019 and received additional radical surgical surgery after endoscopic resection with pathological indication of non-curative resection were collected to analyze the relationship between various factors and the risk of residual cancer or lymph node metastasis after endoscopic resection. Results: Of the 81 patients, 17 (21.0%) were positive for residual cancer or lymph node metastasis, while 64 (79.0%) were negative. Among 17 patients with residual cancer or positive lymph node metastasis, 3 patients had only residual cancer (2 patients with positive vertical cutting edge). 11 patients had only lymph node metastasis, and 3 patients had both residual cancer and lymph node metastasis. Lesion location, poorly differentiated cancer, depth of submucosal invasion ≥2 000 μm, venous invasion were associated with residual cancer or lymph node metastasis after endoscopic (P<0.05). Logistic multivariate regression analysis showed that poorly differentiated cancer (OR=5.513, 95% CI: 1.423, 21.352, P=0.013) was an independent risk factor for residual cancer or lymph node metastasis after endoscopic non-curative resection of early colorectal cancer. Conclusions: For early colorectal cancer after endoscopic non-curable resection, residual cancer or lymph node metastasis is associated with poorly differentiated cancer, depth of submucosal invasion ≥2 000 μm, venous invasion and the lesions are located in the descending colon, transverse colon, ascending colon and cecum with the postoperative mucosal pathology result. For early colorectal cancer, poorly differentiated cancer is an independent risk factor for residual cancer or lymph node metastasis after endoscopic non-curative resection, which is suggested that radical surgery should be added after endoscopic treatment.

Screening methods of SARS-CoV-2 main protease inhibitors and current applications / 药学学报

COVID-19 epidemic continues to spread around the world till these days, and it is urgent to develop more safe and effective new drugs. Due to the limited P3 biosafety laboratories for directly screening inhibitors of virulent viruses with high infectivity, it is necessary to develop rapid and efficient screening methods for viral proteases and other related targets. The main protease (Mpro), which plays a key role in the replication cycle of SARS-CoV-2, is highly conserved and has no homologous proteases in humans, making it an ideal target for drug development. From two different levels, namely, molecular level and cellular level, this paper summarizes the reported screening methods of SARS-CoV-2 Mpro inhibitors through a variety of representative examples, expecting to provide references for further development of SARS-CoV-2 Mpro inhibitors.

Effect of self-efficacy-based intelligent walking training on function of lower extremities of stroke patients / 中国康复理论与实践

ObjectiveTo investigate the effect of self-efficacy-based intelligent walking training on function of lower extremities of stroke patients. MethodsFrom December, 2021 to December, 2022, 44 stroke inpatients from Zhejiang Provincial People's Hospital were randomly divided into control group (n = 22) and experimental group (n = 22). Both groups accepted routine rehabilitation, while the control group accepted routine gait training, and the experimental group accepted self-efficacy-based intelligent walking training on the gait training system (Walker View), for six weeks. They were assessed with Fugl-Meyer Assessment-Lower Extremities, 10-Meter Walk Test, Timed 'Up and Go' Test, stride length and average walking velocity, Functional Ambulation Category and General Self-Efficacy Scale before and after treatment. ResultsThree cases dropped down in the experimental group. All the indexes improved in two groups after treatment (|t| > 5.808, |Z| > 2.961, P < 0.01), and improved more in the experimental group than in the control group (|t| > 2.049, Z = -2.572, P < 0.05). ConclusionThe self-efficacy-based intelligent walking training can promote the recovery of motor function of lower extremities and walking ability in stroke patients.

Correlation between family environment and depressive symptoms among adolescents / 中国学校卫生

Objective@#To understand the relationship between family environment and depressive symptoms among adolescent, and to provide a reference for adolescent mental health promotion and intervention.@*Methods@#From September to December in 2021, a questionnaire survey on family environment and depressive symptoms was conducted among 8 102 middle school students by random cluster sampling method in Shanghai, Urumqi, Changsha and Kunming. The Chi square test was used to compare the depression status of students in different family environments. Multivariate Logistic regression analysis was used to explore the relationship between family environment and depressive symptoms.@*Results@#The detection rates of possible depression, likely depression and severe depression in adolescents were 11.2%, 5.9% and 8.4%, respectively. There were significant differences in the detection rate of depression by gender, academic period, urban and rural areas, family forms and only child statu( χ 2=87.60, 27.19, 6.65, 45.59, 4.78, P <0.05). Logistic regression analysis showed that adolescents in single parent families ( OR =1.45) and reorganized families( OR =1.69) were positively correlated with the occurrence of depressive symptoms compared with those in nuclear families( P <0.01).@*Conclusion@#Compared with nuclear families, the risks of adolescent depressive symptoms in single parent families and reorganized families are higher. Attention should be paid to the mental health education of teenagers from single parents and reorganized families to ensure the development of their physical and mental health.

Optimization of extraction process of Sarcandra glabra by combination of entropy weight method with Box-Behnken response surface method / 中国药房

OBJECTIVE To optimize the extraction process of Sarcandra glabra. METHODS The contents of rosmarinic acid and isofraxidin in S. glabra were determined by HPLC； ultrasonic time， ultrasonic temperature， solid-liquid ratio （mL/g） and methanol volume fraction were investigated by single factor test. Based on the results of single factor test， experimental scheme was designed by Box-Behnken response surface method， and the entropy weight method was used to assign the weight of each index and calculate the comprehensive score. Taking the comprehensive score as the evaluation index， the extraction process of S. glabra was optimized， and then optimized extraction process was verified. RESULTS The optimal extraction technology of S. glabra included ultrasonic time of 40 min， ultrasonic temperature of 45 ℃， liquid-solid ratio of 50∶1， methanol volume fraction of 70%. The results of 3 times of verification experiment showed that average comprehensive score was 0.988 6， and the RSD was 0.50%. The deviation between the actual value and the predicted value （0.985 1） of each comprehensive score was within ±1%. CONCLUSIONS The optimized extraction method is stable， feasible and repeatable， which can provide reference for extraction of S. glabra.

Validation of the detection method for residual human coagulation factor Ⅺ in human prothrombin complex / 中国输血杂志

【Objective】 To establish an enzyme-linked immunosorbent assay (ELISA) method for the determination of residual human coagulation factor Ⅺ in human prothrombin complex and validate the method. 【Methods】 Human factor Ⅺ was reacted with the capture antibody coated on the microtiter plate. After appropriate washing steps, biotinylated primary antibody was bound to the captured protein. Excess primary antibody was washed away and bound antibody was reacted with horseradish peroxidase conjugated streptavidin. TMB substrate was used for color development at 450 nm. The dilution reliability, accuracy, specificity, repeatability, intermediate precision, linearity, range and durability were verified. 【Results】 The verification results showed that the accuracy and specificity of this method met the experimental requirements, with an average recovery rate of 109.2% and RSD of 6.93%. The repeatability RSD was 6.78%, and the intermediate precision RSD was 6.75%, indicating good precision. The linear regression correlation coefficient of standard curve was 0.999 9, showing good accuracy and precision within the linear range. The durability was verified by the incubation time and the validity period of reagent kit opening. The results showed that the RSD of the incubation time change was 6.62%, indicating that the incubation time of this detection method was controlled between 28 to 32 minutes, and there was no significant impact on the results. The RSD of the detection results before and after the reagent kit was opened and stored under conditions for 7 days was 3.84%, indicating that the preservation of the reagent kit according to the conditions for 7 days after opening has no effect on the FⅪ detection results. Both indicated that the method had good durability. The dilution reliability results showed that there was a "hook" effect in the detection of FⅪ residue in human prothrombin complex, which could be solved by diluting 100 to 200 times. 【Conclusion】 This method can be used for the determination of FⅪ residues of human prothrombin complex in laboratory.

Mechanical Thrombectomy for Refractory Cerebral Venous Sinus Thrombosis in a Child with Nephrotic Syndrome : A Case Report

Nephrotic syndrome (NS) is associated with cerebral venous sinus thrombosis (CVST), which is a rare cerebrovascular disorder in children. Systemic anticoagulation with heparin is the standard therapy for CVST, and mechanical thrombectomy (MT) has been described as a salvage treatment for adult anticoagulant refractory CVST, However, it has never been reported in children. We describe a case of MT for refractory CVST in a child with NS. A 13-year-old boy with newly diagnosed NS presented to an emergency department with acute headache. A head computed tomography showed acute thrombus in the superior sagittal sinus, straight sinus and transverse sinus. The child was started on heparin therapy, but clinically deteriorated and became unresponsive. In view of the rapid deterioration of the condition after anticoagulation treatment, the patient received intravascular treatment. Several endovascular technologies, such as stent retriever and large bore suction catheter have been adopted. After endovascular treatment, the patient’s neurological condition was improved within 24 hours, and magnetic resonance venography of the head demonstrated that the CVST was reduced. The child recovered with normal neurological function at discharge. This case highlights the importance of considering MT for refractory CVST, and we suggest that MT may be considered for refractory CVST with NS in children.

Recent advances of antiviral drugs based on multispecific binding strategy / 药学学报

To address the continuous emergence of drug-resistant strains of viruses and the outbreaks of novel virus infections, developing new antiviral drugs based on novel strategies has become an important and urgent research topic. In recent years, the rapidly developing multi-specific binding strategy has become a focus and been widely applied in antiviral. This review summarizes the recent progress of the multi-specific binding strategy in the antiviral field from the perspective of medicinal chemistry and discusses existing challenges as well as future opportunities for antiviral drug discovery.

Recent advances of small molecule inhibitors directly targeting HBV / 药学学报

Hepatitis B virus infection is a serious threat to human life and health. The approved anti-HBV drugs including interferons and nucleos(t)ide analogues have serious adverse effect, rebound phenomena after drug withdrawal, and drug resistance. And the cccDNA cannot be completely eliminated by both of them, which is the reason why a complete cure for hepatitis B cannot be achieved. Therefore, developing anti-HBV drugs directly targeting protein or nucleic acid of HBV remains a current public health priority. Based on the analysis of representative literature from the last decade, this article reviews recent developments in small molecule inhibitors directly targeting HBV from a medicinal chemistry perspective.

Recent advances in small-molecule inhibitors targeting influenza virus glycoproteins / 药学学报

Hemagglutinin and neuraminidase, two important glycoproteins on the surface of influenza virus, play a considerable role in the entry and release stage of the viral life cycle, respectively. With in-depth investigation of influenza virus glycoproteins and the continuous innovation of drug discovery strategies, a new generation of glycoproteins inhibitors have been continuously discovered. From the point of view of medicinal chemistry, this review summarizes the current advances in seeking small-molecule inhibitors targeting influenza virus glycoproteins, hoping to provide valuable guidance for future development of novel antiviral drugs.

Preparation, crystal structure and thermostability of nirmatrelvir polymorphs / 药学学报

The polymorphism and thermostability of nirmatrelvir, the main antiviral component of the oral COVID-19 treatment drug, were studied. Four polymorphs of nirmatrelvir were prepared by recrystallization methods. Among them, Form 1 and nirmatrelvir methyl tert-butyl ether solvate (Form 2) had been reported in the literature, while nirmatrelvir isobutyl acetate solvate (NMTW-IBAC) and nirmatrelvir ethyl acetate solvate (NMTW-EA) are two new solvates. The crystal structures were characterized by single-crystal X-ray diffraction, powder X-ray diffraction, thermogravimetric analysis and differential scanning calorimetry. The thermostability of polymorphism and crystalline transformation were also investigated by combining Hirshfeld surface analysis and interaction energy analysis. The results showed that nirmatrelvir Form 1 belongs orthorhombic crystal system with the space group P212121 and one nirmatrelvir molecule included in the asymmetric unit, which has the same crystal structure as nirmatrelvir Form 4 reported in the literature. Owing to its larger thermal expansion, the differences in crystallographic parameters obtained at different temperatures were found between Form 1 and Form 4. Three solvates of nirmatrelvir belonged to the iso-structural with monoclinic crystal system and the space group P21, in which the asymmetric unit contains one nirmatrelvir molecule and one solvent molecule. The thermal analysis results showed that nirmatrelvir Form 1 was a solvent-free crystal form with the best thermal stability and the strongest intermolecular hydrogen bonding. Among the three solvates, NMTW-EA has the worst thermal stability and the weakest hydrogen bonding interaction between the nirmatrelvir molecule and the solvent molecule. The energy framework of nirmatrelvir solvates showed that the closer the arrangement between solvent and nirmatrelvir molecules, the greater the total interaction energy between solvent and nirmatrelvir molecules. The phase transition studies of the three solvates showed that NMTW-IBAC and NMTW-EA were transformed into amorphous after desolvation, respectively, while Form 2 undergoes oiling during desolvation. The research provides theoretical guidance for the analysis, identification and quality control of nirmatrelvir polymorphs.