Review of animal transmission experiments of respiratory viruses: Implications for transmission risk of SARS-COV-2 in humans via different routes.

Exploring transmission risk of different routes has major implications for epidemic control. However, disciplinary boundaries have impeded the dissemination of epidemic information, have caused public panic about "air transmission," "air-conditioning transmission," and "environment-to-human transmission," and have triggered "hygiene theater." Animal experiments provide experimental evidence for virus transmission, but more attention is paid to whether transmission is driven by droplets or aerosols and using the dichotomy to describe most transmission events. Here, according to characteristics of experiment setups, combined with patterns of human social interactions, we reviewed and grouped animal transmission experiments into four categories-close contact, short-range, fomite, and aerosol exposure experiments-and provided enlightenment, with experimental evidence, on the transmission risk of severe acute respiratory syndrome coronavirus (SARS-COV-2) in humans via different routes. When referring to "air transmission," context should be showed in elaboration results, rather than whether close contact, short or long range is uniformly described as "air transmission." Close contact and short range are the major routes. When face-to-face, unprotected, horizontally directional airflow does promote transmission, due to virus decay and dilution in air, the probability of "air conditioning transmission" is low; the risk of "environment-to-human transmission" highly relies on surface contamination and human behavior based on indirect path of "fomite-hand-mucosa or conjunctiva" and virus decay on surfaces. Thus, when discussing the transmission risk of SARS-CoV-2, we should comprehensively consider the biological basis of virus transmission, environmental conditions, and virus decay. Otherwise, risk of certain transmission routes, such as long-range and fomite transmission, will be overrated, causing public excessive panic, triggering ineffective actions, and wasting epidemic prevention resources.

Improved transfer efficiency of supercharged 36 + GFP protein mediate nucleic acid delivery.

The potential of nucleic acid therapeutics to treat diseases by targeting specific cells has resulted in its increasing number of uses in clinical settings. However, the major challenge is to deliver bio-macromolecules into target cells and/or subcellular locations of interest ahead in the development of delivery systems. Although, supercharged residues replaced protein 36 + GFP can facilitate itself and cargoes delivery, its efficiency is still limited. Therefore, we combined our recent progress to further improve 36 + GFP based delivery efficiency. We found that the penetration efficacy of 36 + GFP protein was significantly improved by fusion with CPP-Dot1l or treatment with penetration enhancer dimethyl sulfoxide (DMSO) in vitro. After safely packaged with plasmid DNA, we found that the efficacy of in vitro and in vivo transfection mediated by 36 + GFP-Dot1l fusion protein is also significantly improved than 36 + GFP itself. Our findings illustrated that fusion with CPP-Dot1l or incubation with DMSO is an alternative way to synergically promote 36 + GFP mediated plasmid DNA delivery in vitro and in vivo.

Sensitive fluorescence detection of pathogens based on target nucleic acid sequence-triggered transcription.

Accurate identification of mutant pathogens derived from genetic polymorphisms is highly desired in clinical diagnosis. However, current detection methods based on Watson-Crick hybridization suffers from false positives due to the cross-reactivity of wild-type sequences. In this study, we developed an accurate identification of mutant pathogens by combining programmable DNAzyme and target nucleic acid sequence-triggered transcription. Single nucleotide variants (SNVs) are the most plentiful type of mutations in the genome. High specificity to discriminate SNV was first achieved by rational design of dual-hairpin DNA structure and DNAzyme's capability of site-specific cleavage. T7 RNA polymerase-mediated transcription amplification was introduced to exponentially increase the sensitivity by encompassing T7 promoter sequence into the dual-hairpin DNA structure. The design of this biosensor is fast and straightforward without many computational steps, and the highly sensitive biosensor can detect not only SNVs but also occasional insertions and large deletions in the genome. We showed that the assay could rapidly detect COVID-19 variant and methicillin-resistant Staphylococcus aureus (MRSA), and the limit of detection is 0.96 copy/µL. The modular design of functional DNA enables this biosensor be easily reconfigured and is useful diagnosis of emerging infectious diseases caused by mutant pathogens.

Study on the decay characteristics and transmission risk of respiratory viruses on the surface of objects.

The complex and changeable environment is a brand-new living condition for the viruses and pathogens released by the infected people to the indoor air or deposited on the surface of objects, which is an important external condition affecting the decay and transmission risk of the viruses. Exposure to contaminated surfaces is one of the main routes of respiratory diseases transmission. Therefore, it is very important for epidemic prevention and control to study the law of virus decay and the environmental coupling effect on various surfaces. Based on the analysis of the influencing mechanism, a large amount of experimental evidence on the survival of viruses on the surface of objects were excavated in this paper, and the effects of various factors, such as surface peripheral temperature, relative humidity, virus-containing droplet volume, surface materials and virus types, on the decay rate constants of viruses were comprehensively analyzed. It was found that although the experimental methods, virus types and experimental conditions varied widely in different experiments, the virus concentrations on the surface of objects all followed the exponential decay law, and the coupling effect of various factors was reflected in the decay rate constant k. Under different experimental conditions, k values ranged from 0.001 to 100 h-1, with a difference of 5 orders of magnitude, corresponding to the characteristic time t99 between 500 and 0.1 h when the virus concentration decreased by 99%. This indicates a large variation in the risk of virus transmission in different scenarios. By revealing the common law and individuality of the virus decay on the surface of objects, the essential relationship between the experimental observation phenomenon and virus decay was analyzed. This paper points out the huge difference in virus transmission risk on the surface at different time nodes, and discusses the prevention and control strategies to grasp the main contradictions in the different situations.

Estimation of the SARS-CoV-2 transmission probability in confined traffic space and evaluation of the mitigation strategies.

Public transport is a fundamental service for the resumption of work and production, but the enclosed environment and dense population create very favorable conditions for the spread of epidemic infections. Thus, effective public health interventions are urgently introduced. The objective of this paper is to quantitatively estimate the SARS-CoV-2 transmission probability and evaluate the influence of environmental parameters and individual intervention on the epidemic prevention. For this purpose, (1) we estimate the virus emission rate with Diamond Princess Cruise Ship infection data by Monte Carlo simulation and the improved Wells-Riley model, and (2) employ the reproductive number R to quantify diverse mitigation strategies. Different determinants are examined such as the duration of exposure, the number of passengers combined with individual interventions such as mask type and mask-wearing rate. The results show that the SARS-CoV-2 quantum generation rate is 185.63. The R shows a stronger positive correlation with the exposure time comparing to the number of passengers. In this light, reducing the frequency of long-distance journeys on crowded public transportation may be required to reduce the spread of the virus during the pandemic. N95 mask and surgical mask can reduce the transmission risk by 97 and 84%, respectively, and even homemade mask can reduce the risk by 67%, which indicates that it is necessary to advocate wearing masks on public transportation.

COVID-19 epidemic prediction and the impact of public health interventions: A review of COVID-19 epidemic models.

The coronavirus disease outbreak of 2019 (COVID-19) has been spreading rapidly to all corners of the word, in a very complex manner. A key research focus is in predicting the development trend of COVID-19 scientifically through mathematical modelling. We conducted a systematic review of epidemic prediction models of COVID-19 and the public health intervention strategies by searching the Web of Science database. 55 studies of the COVID-19 epidemic model were reviewed systematically. It was found that the COVID-19 epidemic models were different in the model type, acquisition method, hypothesis and distribution of key input parameters. Most studies used the gamma distribution to describe the key time period of COVID-19 infection, and some studies used the lognormal distribution, the Erlang distribution, and the Weibull distribution. The setting ranges of the incubation period, serial interval, infectious period and generation time were 4.9-7 days, 4.41-8.4 days, 2.3-10 days and 4.4-7.5 days, respectively, and more than half of the incubation periods were set to 5.1 or 5.2 days. Most models assumed that the latent period was consistent with the incubation period. Some models assumed that asymptomatic infections were infectious or pre-symptomatic transmission was possible, which overestimated the value of R0. For the prediction differences under different public health strategies, the most significant effect was in travel restrictions. There were different studies on the impact of contact tracking and social isolation, but it was considered that improving the quarantine rate and reporting rate, and the use of protective face mask were essential for epidemic prevention and control. The input epidemiological parameters of the prediction models had significant differences in the prediction of the severity of the epidemic spread. Therefore, prevention and control institutions should be cautious when formulating public health strategies by based on the prediction results of mathematical models.

SARS-CoV-2 Disrupts Splicing, Translation, and Protein Trafficking to Suppress Host Defenses.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified coronavirus that causes the respiratory disease known as coronavirus disease 2019 (COVID-19). Despite the urgent need, we still do not fully understand the molecular basis of SARS-CoV-2 pathogenesis. Here, we comprehensively define the interactions between SARS-CoV-2 proteins and human RNAs. NSP16 binds to the mRNA recognition domains of the U1 and U2 splicing RNAs and acts to suppress global mRNA splicing upon SARS-CoV-2 infection. NSP1 binds to 18S ribosomal RNA in the mRNA entry channel of the ribosome and leads to global inhibition of mRNA translation upon infection. Finally, NSP8 and NSP9 bind to the 7SL RNA in the signal recognition particle and interfere with protein trafficking to the cell membrane upon infection. Disruption of each of these essential cellular functions acts to suppress the interferon response to viral infection. Our results uncover a multipronged strategy utilized by SARS-CoV-2 to antagonize essential cellular processes to suppress host defenses.