Preventive and therapeutic benefits of nelfinavir in rhesus macaques and human beings infected with SARS-CoV-2

Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2.Here we report that nelfinavir,an FDA approved drug for the treatment of HIV infection,is effective against SARS-CoV-2 and COVID-19.Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2(IC50=8.26μM),while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93μM(EC50).In comparison with vehicle-treated animals,rhesus macaque prophylactically treated with nelfinavir had significantly lower temperature and significantly reduced virus loads in the nasal and anal swabs of the animals.At necropsy,nelfinavir-treated animals had a significant reduction of the viral replication in the lungs by nearly three orders of magnitude.A prospective clinic study with 37 enrolled treatment-naive patients at Shanghai Public Health Clinical Center,which were randomized(1:1)to nelfinavir and control groups,showed that the nelfinavir treatment could shorten the duration of viral shedding by 5.5 days(9.0 vs.14.5 days,P=0.055)and the duration of fever time by 3.8 days(2.8 vs.6.6 days,P=0.014)in mild/moderate COVID-19 patients.The antiviral efficiency and clinical benefits in rhesus macaque model and in COVID-19 patients,together with its well-established good safety profile in almost all ages and during pregnancy,indicated that nelfinavir is a highly promising medication with the potential of preventative effect for the treatment of COVID-19.

A real-time and modular approach for quick detection and mechanism exploration of DPIs with different carrier particle sizes

Dry powder inhalers(DPIs) had been widely used in lung diseases on account of direct pulmonary delivery, good drug stability and satisfactory patient compliance. However, an indistinct understanding of pulmonary delivery processes(PDPs) hindered the development of DPIs. Most current evaluation methods explored the PDPs with over-simplified models, leading to uncompleted investigations of the whole or partial PDPs. In the present research, an innovative modular process analysis platform(MPAP) was applied to investigate the detailed mechanisms of each PDP of DPIs with different carrier particle sizes(CPS). The MPAP was composed of a laser particle size analyzer, an inhaler device,an artificial throat and a pre-separator, to investigate the fluidization and dispersion, transportation,detachment and deposition process of DPIs. The release profiles of drug, drug aggregation and carrier were monitored in real-time. The influence of CPS on PDPs and corresponding mechanisms were explored. The powder properties of the carriers were investigated by the optical profiler and Freeman Technology four powder rheometer. The next generation impactor was employed to explore the aerosolization performance of DPIs. The novel MPAP was successfully applied in exploring the comprehensive mechanism of PDPs, which had enormous potential to be used to investigate and develop DPIs.

Unusual global outbreak of monkeypox:what should we do?

Recently,monkeypox has become a global concern amid the ongoing COVID-19 pandemic.Monkeypox is an acute rash zoonosis caused by the monkeypox virus,which was previously concentrated in Africa.The re-emergence of this pathogen seems unusual on account of outbreaks in multiple nonendemic countries and the incline to spread from person to person.We need to revisit this virus to prevent the epidemic from getting worse.In this review,we comprehensively summarize studies on monkeypox,including its epidemiology,biological characteristics,pathogenesis,and clinical characteristics,as well as therapeutics and vaccines,highlighting its unusual outbreak attributed to the transformation of transmission.We also analyze the present situation and put forward countermeasures from both clinical and scientific research to address it.

Recombinant human interferon-α1b inhibits SARS-CoV-2 better than interferon-α2b in vitro

Dear Editor,The coronavirus disease 2019(COVID-19)outbreak,has spread across the world(Wu et al.,2020).The causative agent of COVID-19,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is highly pathogenic and infectious,which become a major public health hazard that has had a devastating social and economic impact worldwide(Li Q.Q.et al.,2020).Variants of the virus have emerged that behave differently(CDC2021;Gobeil et al.,2020;Leung et al.,2021).Some of them show increased infectivity(Li Q.et al.,2020;Zhang et al.,2020)and may escape from neutralizing antibodies(Weisblum et al.,2020).

Correlation of Oral Microbiota With Different Immune Responses to Antiretroviral Therapy in People Living With HIV

Both HIV infection and antiretroviral therapy(ART)affect the oral microbiome.Whether successful treatment with ART in people living with HIV(PLWH),which leads to a significant decline in viral loads and immune reconstitution,is associated with changes in or recovery of the oral microbiome remains unknown.Therefore,we performed a cross-sectional study of 118 PLWH receiving regular ART and 40 healthy controls(HCs).Among the 118 PLWH,18 immunological nonresponders(INRs;<200 CD4^(+)T cells/μL)and 30 immunological responders(IRs;≥500 CD4^(+)T cells/μL)were identified.The oral microbiota composition of all participants was analyzed using 16S rRNA gene sequencing of throat swab samples.Relative abundance of bacterial genera was compared between IRs and INRs,and Pearson correlations between bacterial abundance and peripheral blood immune cell counts were evaluated.The INR group showed lower alpha diversity than the IR and HC groups,which displayed similar alpha diversity.The genera Alloprevotella,Prevotella and Neisseria were more abundant in PLWH than in HCs,whereas the genera Rothia,Streptococcus and Fusobacterium were more abundant in HCs than in PLWH.The genus Rothia was more abundant in the INR group,whereas Prevotella,Alloprevotella,Porphyromonas and Haemophilus were more abundant in the IR group.The genera Rothia and Alloprevotella were negatively and positively associated with CD4^(+)T cell counts,respectively.Thus,an increased abundance of Rothia in the oral microbiome is associated with unfavorable outcomes regarding immune reconstitution in PLWH receiving regular ART,whereas Prevotella,Alloprevotella,Porphyromonas and Haemophilus are associated with favorable outcomes.