Influenza is an important research subject around the world because of its threat to humanity. Influenza A virus (IAV) causes seasonal epidemics and sporadic, but dangerous pandemics. A rapid antigen changes and recombination of the viral RNA genome contribute to the reduced effectiveness of vaccination and anti-influenza drugs. Hence, there is a necessity to develop new antiviral drugs and strategies to limit the influenza spread. IAV is a single-stranded negative sense RNA virus with a genome (viral RNA—vRNA) consisting of eight segments. Segments within influenza virion are assembled into viral ribonucleoprotein (vRNP) complexes that are independent transcription-replication units. Each step in the influenza life cycle is regulated by the RNA and is dependent on its interplay and dynamics. Therefore, viral RNA can be a proper target to design novel therapeutics. Here, we briefly described examples of anti-influenza strategies based on the antisense oligonucleotide (ASO), small interfering RNA (siRNA), microRNA (miRNA) and catalytic nucleic acids. In particular we focused on the vRNA structure-function relationship as well as presented the advantages of using secondary structure information in predicting therapeutic targets and the potential future of this field.
2 May 2023 in Cellular and Molecular Life Sciences
Influenza A virus (IAV) is a respiratory virus that causes epidemics and pandemics. Knowledge of IAV RNA secondary structure in vivo is crucial for a better understanding of virus biology. Moreover, it is a fundament for the development of new RNA-targeting antivirals. Chemical RNA mapping using selective 2’-hydroxyl acylation analyzed by primer extension (SHAPE) coupled with Mutational Profiling (MaP) allows for the thorough examination of secondary structures in low-abundance RNAs in their biological context. So far, the method has been used for analyzing the RNA secondary structures of several viruses including SARS-CoV-2 in virio and in cellulo. Here, we used SHAPE-MaP and dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq) for genome-wide secondary structure analysis of viral RNA (vRNA) of the pandemic influenza A/California/04/2009 (H1N1) strain in both in virio and in cellulo environments. Experimental data allowed the prediction of the secondary structures of all eight vRNA segments in virio and, for the first time, the structures of vRNA5, 7, and 8 in cellulo. We conducted a comprehensive structural analysis of the proposed vRNA structures to reveal the motifs predicted with the highest accuracy. We also performed a base-pairs conservation analysis of the predicted vRNA structures and revealed many highly conserved vRNA motifs among the IAVs. The structural motifs presented herein are potential candidates for new IAV antiviral strategies.
In comparison to other European countries, during the first months of the COVID-19 pandemic, Poland reported a relatively low number of confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. To estimate the scale of the pandemic in Poland, a serosurvey of antibodies against SARS-CoV-2 was performed after the first wave of COVID-19 in Europe (March–May 2020). Within this study, we collected samples from 28 July to 24 September 2020 and, based on the ELISA results, we found that 1.67% (25/1500, 95% CI 1.13–2.45) of the Poznan (Poland) metropolitan area’s population had antibodies against SARS-CoV-2 after the first wave of COVID-19. However, the presence of anti-SARS-CoV-2 IgG antibodies was confirmed with immunoblotting in 56% (14/25) samples, which finally resulted in a decrease in seroprevalence, i.e., 0.93% (14/1500, 95% CI 0.56–1.56). The positive anti-SARS-CoV-2 IgG results were associated with age, occupation involving constant contact with people, travelling abroad, non-compliance with epidemiological recommendations and direct contact with the novel coronavirus. Our findings confirm the low SARS-CoV-2 incidence in Poland and imply that the population had little herd immunity heading into the second and third wave of the pandemic, and therefore, that herd immunity contributed little to preventing the high numbers of SARS-CoV-2 infections and COVID-19-related deaths in Poland during these subsequent waves.
In comparison to other European countries, during the first months of COVID-19 pandemic, Poland reported relatively low number of confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. To estimate the scale of pandemic in Poland, a serosurvey of antibodies against SARS-CoV-2 was performed after the first wave of COVID-19 in Europe (March – May 2020). Within this study, we collected samples from July 28 to September 24, 2020 and based on the ELISA results, we found that 1.67% (25/1500, 95%CI 1.13 - 2.45) of the Poznan (Poland) metropolitan area’s population had antibodies against SARS-CoV-2 after the first wave of COVID-19. However, the presence of anti-SARS-CoV-2 IgG antibodies was confirmed with immunoblot in 56% (14/25) samples, what finally resulted in decrease of seroprevalence, i.e. 0.93% (14/1500, 95%CI 0.56 - 1.56). The positive anti-SARS-CoV-2 IgG results were associated with age, occupation related to constant contact with people, travelling abroad, non-compliance with epidemiological recommendations and direct contact with the novel coronavirus. Our findings confirm the low SARS-CoV-2 incidence in Poland and imply that the population had little herd immunity heading into the second and third wave of the pandemic, and therefore herd immunity contributed little to prevent the high numbers of SARS-CoV-2 infections and COVID-19 related deaths in Poland during these subsequent waves.
One of the groups most vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is healthcare workers (HCWs) who have direct contact with suspected and confirmed coronavirus diseases 2019 (COVID-19) patients. Therefore, this study aimed to (i) conduct a longitudinal analysis of the seroprevalence of SARS-CoV-2 infection among HCWs working in two healthcare units (HCUs) in Poland and (ii) identify anti-SARS-CoV-2 IgG antibody (Ab) response factors following infection and anti-COVID-19 vaccination. The overall seroprevalence increased from 0% at baseline in September 2020 to 37.8% in December 2020. It reached 100% in February 2021 after BNT126b2 (Pfizer New York, NY, USA/BioNTech Mainz, Germany) full vaccination and declined to 94.3% in September 2021. We observed significant differences in seroprevalence between the tested high- and low-risk infection HCUs, with the highest seropositivity among the midwives and nurses at the Gynecology and Obstetrics Ward, who usually have contact with non-infectious patients and may not have the proper training, practice and personal protective equipment to deal with pandemic infections, such as SARS-CoV-2. We also found that anti-SARS-CoV-2 Ab levels after coronavirus infection were correlated with disease outcomes. The lowest Ab levels were found among HCWs with asymptomatic coronavirus infections, and the highest were found among HCWs with severe COVID-19. Similarly, antibody response after vaccination depended on previous SARS-CoV-2 infection and its course: the highest anti-SARS-CoV-2 Ab levels were found in vaccinated HCWs after severe COVID-19. Finally, we observed an approximately 90–95% decrease in anti-SARS-CoV-2 Ab levels within seven months after vaccination. Our findings show that HCWs have the highest risk of SARS-CoV-2 infection, and due to antibody depletion, extra protective measures should be undertaken. In addition, in the context of the emergence of new pathogens with pandemic potential, our results highlight the necessity for better infectious disease training and regular updates for the low infection risk HCUs, where the HCWs have only occasional contact with infectious patients.
During the COVID-19 pandemic, several vaccines were developed to limit the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, due to SARS-CoV-2 mutations and uneven vaccination coverage among populations, a series of COVID-19 waves have been caused by different variants of concern (VOCs). Despite the updated vaccine formulations for the new VOC, the benefits of additional COVID-19 vaccine doses have raised many doubts, even among high-risk groups such as healthcare workers (HCWs). We examined the factors underlying hesitancy to receive COVID-19 booster vaccine doses and analysed the anti-SARS-CoV-2 IgG antibody response after booster vaccination among HCWs. Our study found that 42% of the HCWs were hesitant about the second booster dose, while 7% reported no intent to get vaccinated with any additional doses. As reasons for not vaccinating, participants most frequently highlighted lack of time, negative experiences with previous vaccinations, and immunity conferred by past infections. In addition, we found the lowest post-vaccination antibody titres among HCWs who did not receive any vaccine booster dose and the highest among HCWs vaccinated with two booster doses.