Inhibition of SARS-CoV-2 Replication by Self-Assembled siRNA Nanoparticles Targeting Multiple Highly Conserved Viral Sequences.

Coronavirus infectious disease 2019 (COVID-19), caused by severe acute respiratory virus type 2 (SARS-CoV-2), has caused a global public health crisis. As an RNA virus, the high gene mutability of SARS-CoV-2 poses significant challenges to the development of broad-spectrum vaccines and antiviral therapeutics. There remains a lack of specific therapeutics directly targeting SARS-CoV-2. With the ability to efficiently inhibit the expression of target genes in a sequence-specific way, small interfering RNA (siRNA) therapy has exhibited significant potential in antiviral and other disease treatments. In this work, we presented a highly effective self-assembled siRNA nanoparticle targeting multiple highly conserved regions of SARS-CoV-2. The siRNA sequences targeting viral conserved regions were first screened and evaluated by their thermodynamic features, off-target effects, and secondary structure toxicities. RNA motifs including siRNA sequences were then designed and self-assembled into siRNA nanoparticles. These siRNA nanoparticles demonstrated remarkable uniformity and stability and efficiently entered cells directly through cellular endocytic pathways. Moreover, these nanoparticles effectively inhibited the replication of SARS-CoV-2, exhibiting a superior inhibitory effect compared to free siRNA. These results demonstrated that these self-assembled siRNA nanoparticles targeting highly conserved regions of SARS-CoV-2 represent highly effective antiviral candidates for the treatment of infections, and are promisingly effective against current and future viral variants.

Knowledge, attitude, and practice regarding pharmacovigilance among the general public in Western China: a cross-sectional study.

OBJECTIVES: Spontaneous reporting of adverse drug reactions (ADRs) to pharmacovigilance centers is a common and inexpensive method of ADR detection. Although China requires patients to report ADRs directly, the reporting rate is extremely low. We assessed public knowledge, attitudes, and practice (KAP) regarding pharmacovigilance in Shaanxi Province, China. METHODS: A self-administered questionnaire to evaluate the KAP of the general public regarding pharmacovigilance was designed and distributed in selected locations throughout Xi'an. The data were double input and statistical methods were used to analyze questionnaire responses. RESULTS: Knowledge scores among consumers regarding pharmacovigilance was low. Women and respondents in younger age groups had high knowledge scores. Over 85.0% of respondents had a positive attitude toward ADR monitoring. Most respondents said they would voluntarily report ADR to medical personnel, and 85.1% said they would report ADRs with easier policies. Further, 89.1% of respondents preferred reporting ADRs by phone or online whereas 10.9% preferred email or post. Regarding reasons for not reporting ADRs, 57.8 and 43.6% of respondents, respectively, did not know to whom to give feedback and felt that ADRs were not serious enough to report. Respondents had difficulty with portions of the ADR reporting form addressing drug information and description of ADR signals. CONCLUSIONS: The public has poor awareness about, but a positive attitude toward, pharmacovigilance. Unclear feedback pathways and lack of understanding about the seriousness of ADRs were the main reasons patients did not report ADRs, and respondents had difficulty with parts of the reporting form. The government should publicize the importance of ADR monitoring and develop more suitable forms and measures for patients to report ADR.