The devastating COVID-19 pandemic has caused more than six million deaths worldwide during the last 2 years. Effective therapeutic agents are greatly needed, yet promising magic bullets still do not exist. Numerous natural products (cordycepin, gallinamide A, plitidepsin, telocinobufagin, and tylophorine) have been widely studied and play a potential function in treating COVID-19. In this paper, we reviewed published studies (from May 2021 to April 2022) relating closely to bioactive natural products (isolated from medicinal plants, animals products, and marine organisms) in COVID-19 therapy in vitro to provide some essential guidance for anti-SARS-CoV-2 drug research and development.

Bioactive natural products in COVID-19 therapy

Isolation, contact tracing and restrictions on social movement are being globally implemented to prevent and control onward spread of SARS-CoV-2, even though the infection risk modelled on RNA detection by RT-qPCR remains biased as viral shedding and infectivity are not discerned. Thus, we aimed to develop a rapid viability RT-qPCR procedure to infer SARS-CoV-2 infectivity in clinical specimens and environmental samples. We screened monoazide dyes and platinum compounds as viability molecular markers on five SARS-CoV-2 RNA targets. A platinum chloride-based viability RT-qPCR was then optimized using genomic RNA, and inactivated SARS-CoV-2 particles inoculated in buffer, stool, and urine. Our results were finally validated in nasopharyngeal swabs from persons who tested positive for COVID-19 and in wastewater samples positive for SARS-CoV-2 RNA. We established a rapid viability RT-qPCR that selectively detects potentially infectious SARS-CoV-2 particles in complex matrices. In particular, the confirmed positivity of nasopharyngeal swabs following the viability procedure suggests their potential infectivity, while the complete prevention of amplification in wastewater indicated either non-infectious particles or free RNA. The viability RT-qPCR approach provides a more accurate ascertainment of the infectious viruses detection and it may complement analyses to foster risk-based investigations for the prevention and control of new or re-occurring outbreaks with a broad application spectrum.

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Platinum chloride-based viability RT-qPCR for SARS-CoV-2 detection in complex samples.

Abstract The outbreak of COVID-19 has become a global crisis, and brought severe disruptions to societies and economies. Until now, effective therapeutics against COVID-19 are in high demand. Along with our improved understanding of the structure, function, and pathogenic process of SARS-CoV-2, many small molecules with potential anti-COVID-19 effects have been developed. So far, several antiviral strategies were explored. Besides directly inhibition of viral proteins such as RdRp and M pro , interference of host enzymes including ACE2 and proteases, and blocking relevant immunoregulatory pathways represented by JAK/STAT, BTK, NF-κB, and NLRP3 pathways, are regarded feasible in drug development. The development of small molecules to treat COVID-19 has been achieved by several strategies, including computer-aided lead compound design and screening, natural product discovery, drug repurposing, and combination therapy. Several small molecules representative by remdesivir and paxlovid have been proved or authorized emergency use in many countries. And many candidates have entered clinical-trial stage. Nevertheless, due to the epidemiological features and variability issues of SARS-CoV-2, it is necessary to continue exploring novel strategies against COVID-19. This review discusses the current findings in the development of small molecules for COVID-19 treatment. Moreover, their detailed mechanism of action, chemical structures, and preclinical and clinical efficacies are discussed. 

/pdf/small-molecules-in-the-treatment-of-covid-19-313d7e1y.pdf

Small molecules in the treatment of COVID-19

The COVID-19 pandemic has caused at least 508,827,830 infections and is associated with a 1.2% mortality rate worldwide (1). New SARS-CoV-2 variants have driven new waves of the pandemic as a result of their increased transmissibility and ability to evade the immune response (2). The post-acute sequelae of SARS-CoV-2 infection (PASC) is an important but underestimated public health issue that can have a long-term impact on pulmonary and multiple extrapulmonary tissues and organs through several potential mechanisms (3, 4). Recent studies demonstrate that approximately 4–69% of patients (including children, adolescents, adults, and senior) suffer from PASC (5–11). There is considerable evidence concerning post-acute sequelae that will likely outlast the current pandemic and need to be addressed. This article reviews the clinical sequelae of COVID-19 survivors and provides valuable insights required to fill the gaps in medical knowledge.

/pdf/post-acute-sequelae-of-sars-cov-2-infection-a-neglected-1mgs7qhu.pdf

Post-acute Sequelae of SARS-CoV-2 Infection: A Neglected Public Health Issue

The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global public health disaster. The current gold standard for the diagnosis of infected patients is real-time reverse transcription-quantitative PCR (RT-qPCR). SUMMARY The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global public health disaster. The current gold standard for the diagnosis of infected patients is real-time reverse transcription-quantitative PCR (RT-qPCR). As effective as this method may be, it is subject to false-negative and -positive results, affecting its precision, especially for the detection of low viral loads in samples. In contrast, digital PCR (dPCR), the third generation of PCR, has been shown to be more effective than the gold standard, RT-qPCR, in detecting low viral loads in samples. In this review article, we selected publications to show the broad-spectrum applications of dPCR, including the development of assays and reference standards, environmental monitoring, mutation detection, and clinical diagnosis of SARS-CoV-2, while comparing it analytically to the gold standard, RT-qPCR. In summary, it is evident that the specificity, sensitivity, reproducibility, and detection limits of RT-dPCR are generally unaffected by common factors that may affect RT-qPCR. As this is the first time that dPCR is being tested in an outbreak of such a magnitude, knowledge of its applications will help chart a course for future diagnosis and monitoring of infectious disease outbreaks.

Digital PCR Applications in the SARS-CoV-2/COVID-19 Era: a Roadmap for Future Outbreaks

Natural triterpenoids from licorice potently inhibit SARS-CoV-2 infection

Rapid determination of infectious SARS-CoV-2 in PCR-positive samples by SDS-PMA assisted RT-qPCR.

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/coronavirus disease 2019 (COVID-19) pandemic has crippled several countries across the globe posing a serious global public health challenge. Despite the massive rollout of vaccines, molecular diagnosis remains the most important method for timely isolation, diagnosis, and control of COVID-19. Several molecular diagnostic tools have been developed since the beginning of the pandemic with some even gaining emergency use authorization (EUA) from the United States (US) Food and Drug Administration (FDA) for in vitro diagnosis of SARS-CoV-2. Herein, we discuss the working principles of some commonly used molecular diagnostic tools for SARS-CoV-2 including nucleic acid amplification tests (NAATs), isothermal amplification tests (IATs), and rapid diagnostic tests (RDTs). To ensure successful detection while minimizing the risk of cross-infection and misdiagnosis when using these diagnostic tools, laboratories should adhere to proper biosafety practices. Hence, we also present the common biosafety practices that may ensure the successful detection of SARS-CoV-2 from specimens while protecting laboratory workers and non-suspecting individuals from being infected. From this review article, it is clear that the SARS-CoV-2 pandemic has led to an increase in molecular diagnostic tools and the formation of new biosafety protocols that may be important for future and ongoing outbreaks.

SARS-CoV-2/COVID-19 Laboratory Biosafety Practices and Current Molecular Diagnostic Tools.

The invention relates to the technical field of genetic engineering and particularly relates to a streptococcus broad-spectrum chimeric lyase GBS-V12b and a coding gene and application thereof The streptococcus broad-spectrum chimeric lyase GBS-V12b has an amino acid sequence shown in SEQ ID No 1 The coding gene of the streptococcus broad-spectrum chimeric lyase GBS-V12b has a nucleotide sequence shown in SEQ ID No 2 The streptococcus broad-spectrum chimeric lyase GBS-V12b disclosed by the invention can be used for killing a variety of streptococci and staphylococci, particularly streptococcus pneumoniae, streptococcus pyogenes, streptococcus suis, streptococcus agalactiae, streptococcus dysgalactiae, streptococcus mutans, streptococcus iniae, and a variety of enterococci and staphylococcus aureus; the GBS-V12b is good in stability and is insensitive to high-concentration NaCl; the recombinant protein GBS-V12b can be excellently expressed in Escherichia coli BL21 (DE3); high-dosage GBS-V12b is free of obvious cytotoxicity Therefore, the GBS-V12b can be used for controlling a variety of streptococci and treating infections caused by the streptococci independently or as an additive, thereby having a broad application prospect

Streptococcus broad-spectrum chimeric lyase GBS-V12b and coding gene and application thereof

The invention relates to the technical field of gene engineering, in particular to novel broad-spectrum chimeric lysin BGS-PlySb and an encoding gene and application thereof. The novel broad-spectrum chimeric lysin BGS-PlySb has an amino acid sequence shown as in SEQ ID NO. 1; the encoding gene of the novel broad-spectrum chimeric lysin BGS-PlySb has a nucleotide sequence shown as in SEQ ID NO. 2. A novel chimeric lysin is constructed by means of gene splicing and is suitable for killing various species of Streptococcus and Staphylococcus, particularly various species of Enterococcus, and Staphylococcus aureus, as well as Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus suis, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus mutans, Streptococcus iniae and other species; the novel broad-spectrum chimeric lysin BGS-PlySb has good stability and is insensitive to high-concentration NaCl, recombinant protein GBS-PlySb is well expressible in Escherichia coli BL21 (DE3), and a high dose of GBS-PlySb is free of significant cytotoxicity. Therefore, the novel broad-spectrum chimeric lysin BGS-PlySb is applicable independently to or as an additive to the control of various species of Streptococcus and the treatment of infections caused by these species, and has a promising application prospect.

Hong Wei

Papers

Natural triterpenoids from licorice potently inhibit SARS-CoV-2 infection

Rapid determination of infectious SARS-CoV-2 in PCR-positive samples by SDS-PMA assisted RT-qPCR.

SARS-CoV-2/COVID-19 Laboratory Biosafety Practices and Current Molecular Diagnostic Tools.

Streptococcus broad-spectrum chimeric lyase GBS-V12b and coding gene and application thereof

Novel broad-spectrum chimeric lysin BGS-PlySb and encoding gene and application thereof