Clustered regularly interspaced short palindromic repeats, a glimpse – impacts in molecular biology, trends and highlights

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) is a novel molecular tool. In recent days, it has been highlighted a lot, as the Nobel prize was awarded for this sector in 2020, and also for its recent use in Covid-19 related diagnostics. Otherwise, it is an eminent gene-editing technique applied in diverse medical zones of therapeutics in genetic diseases, hematological diseases, infectious diseases, etc., research related to molecular biology, cancer, hereditary diseases, immune and inflammatory diseases, etc., diagnostics related to infectious diseases like viral hemorrhagic fevers, Covid-19, etc. In this review, its discovery, working mechanisms, challenges while handling the technique, recent advancements, applications, alternatives have been discussed. It is a cheaper, faster technique revolutionizing the medicinal field right now. However, their off-target effects and difficulties in delivery into the desired cells make CRISPR, not easily utilizable. We conclude that further robust research in this field may promise many interesting, useful results.

Viral-induced inflammatory coagulation disorders: Preparing for another epidemic

A number of viral infectious diseases have emerged or reemerged from wildlife vectors that have generated serious threats to global health. Increased international traveling and commerce increase the risk of transmission of viral or other infectious diseases. In addition, recent climate changes accelerate the potential spread of domestic disease. The Coronavirus disease 2019 (COVID-19) pandemic is an important example of the worldwide spread, and the current epidemic will unlikely be the last. Viral hemorrhagic fevers, such as Dengue and Lassa fevers, may also have the potential to spread worldwide with a significant impact on public health with unpredictable timing. Based on the important lessons learned from COVID-19, it would be prudent to prepare for future pandemics of life-threatening viral diseases. Among the various threats, this review focuses on the coagulopathy of acute viral infections since hypercoagulability has been a major challenge in COVID-19, but represents a different presentation compared to viral hemorrhagic fever. However, both thrombosis and hemorrhage are understood as the result of thromboinflammation due to viral infections, and the role of anticoagulation is important to consider.

Structural landscape of the complete genomes of dengue virus serotypes and other viral hemorrhagic fevers

Background With more than 300 million potentially infected people every year, and with the expanded habitat of mosquitoes due to climate change, Dengue virus (DENV) cannot be considered anymore only a tropical disease. The RNA secondary structure is a functional characteristic of RNA viruses, and together with the accumulated high-throughput sequencing data could provide general insights towards understanding virus biology. Here, we profiled the RNA secondary structure of > 7000 complete viral genomes from 11 different species focusing on viral hemorrhagic fevers, including DENV serotypes, EBOV, and YFV. Results In our work we demonstrated that the secondary structure and presence of protein-binding domains in the genomes can be used as intrinsic signature to further classify the viruses. With our predictive approach, we achieved high prediction scores of the secondary structure (AUC up to 0.85 with experimental data), and computed consensus secondary structure profiles using hundreds of in silico models. We observed that viruses show different structural patterns, where e.g., DENV-2 and Ebola virus tend to be less structured than the other viruses. Furthermore, we observed virus-specific correlations between secondary structure and the number of interaction sites with human proteins, reaching a correlation of 0.89 in the case of Zika virus. We also identified that helicases-encoding regions are more structured in several flaviviruses, while the regions encoding for the contact proteins exhibit virus-specific clusters in terms of RNA structure and potential protein-RNA interactions. We also used structural data to study the geographical distribution of DENV, finding a significant difference between DENV-3 from Asia and South-America, where the structure is also driving the clustering more than sequence identity, which could imply different evolutionary routes of this subtype. Conclusions Our massive computational analysis provided novel results regarding the secondary structure and the interaction with human proteins, not only for DENV serotypes, but also for other flaviviruses and viral hemorrhagic fevers-associated viruses. We showed how the RNA secondary structure can be used to categorise viruses, and even to further classify them based on the interaction with proteins. We envision that these approaches can be used to further classify and characterise these complex viruses.

Residual and Late Onset Symptoms Appeared in a Patient with Severe Fever with Thrombocytopenia in a Convalescence Stage

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by Dabie bandavirus (formerly SFTS virus, SFTSV). Its manifestations during the convalescent phase have not been widely described. We report a patient presenting with hematospermia, fatigue, myalgia, alopecia, insomnia, and depression during the recovery phase of SFTS. Since these symptoms are widely observed in patients with viral hemorrhagic fevers, there might be common mechanisms between SFTS and other viral hemorrhagic fevers. Close monitoring may be required during the recovery phase of SFTS.

Remote-Controlled and Pulse Pressure–Guided Fluid Treatment for Adult Patients with Viral Hemorrhagic Fevers

ABSTRACTCirculatory shock, caused by severe intravascular volume depletion resulting from gastrointestinal losses and profound capillary leak, is a common clinical feature of viral hemorrhagic fevers, including Ebola virus disease, Marburg hemorrhagic fever, and Lassa fever. These conditions are associated with high case fatality rates, and they carry a significant risk of infection for treating personnel. Optimized fluid therapy is the cornerstone of management of these diseases, but there are few data on the extent of fluid losses and the severity of the capillary leak in patients with VHFs, and no specific guidelines for fluid resuscitation and hemodynamic monitoring exist. We propose an innovative approach for monitoring VHF patients, in particular suited for low-resource settings, facilitating optimizing fluid therapy through remote-controlled and pulse pressure–guided fluid resuscitation. This strategy would increase the capacity for adequate supportive care, while decreasing the risk for virus transmission to health personnel.

Elevated l-threonine is a biomarker for Lassa fever and Ebola

Background Lassa fever and Ebola are characterized by non-specific initial presentations that can progress to severe multisystem illnesses with high fatality rates. Samples from additional subjects are examined to extend and corroborate biomarkers with prognostic value for these diseases. Methods Liquid Chromatography Mass Spectrometry metabolomics was used to identify and confirm metabolites disrupted in the blood of Lassa fever and Ebola patients. Authenticated standards are used to confirm the identify of key metabolites. Results We confirm prior results by other investigators that the amino acid l-threonine is elevated during Ebola virus infection. l-Threonine is also elevated during Lassa virus infection. We also confirmed that platelet-activating factor (PAF) and molecules with PAF moiety are reduced in the blood of patients with fatal Lassa fever. Similar changes in PAF and PAF-like molecules were not observed in the blood of Ebola patients. Conclusions Metabolomics may provide tools to identify pathways that are differentially affected during viral hemorrhagic fevers and guide development of diagnostics to monitor and predict outcome.