Category Technology

A group of La Paz University Essential, Spain has suggested a treatment based on the novel coronavirus (COVID-19) symptoms that can be completely mimicked by a protein cocktail of SARS-CoV-2.
https://pubmed.ncbi.nlm.nih.gov/33283062/

In patients with COVID-19, inflammation and cytokine storms are induced, and il-1β, IL-6, and TNF-α are known to be highly expressed. This early stage can be explained by excessive activation of monocytes and macrophages. In the later stages of COVID-19, adaptive immunity plays a critical role, and in severe patients, lymphocytes are significantly reduced.

Blood cells obtained from healthy people was incubated with SARS-CoV-2 S-protein, N-protein and P-protein cocktails and developed a phenotype that mimics the COVID-19 condition. For example, in monocytes, HLA-DR, the signal path for antigen presentation, was reduced, and PD-L1, a immune checkpoint ligand, was highly expressed.
From these results, it was suggested that the use of inhibitors (antibodies) for immune checkpoint molecules could lead to effective treatment. Actually, a clinical trial using camrelizumab (PD-1 antibody) is in progress.

Expect progress.

RT-PCR is used as you know to test for suspected infection of the new coronavirus (SARS-CoV-2). Sensitivity and specificity are very important in testing, but there are some doubts as to how high the generally implemented RT-PCR could detect SARS-CoV-2 without cross-reactivity to other coronaviruses including influenza viruses. Therefore, the following groups have reported a novel methodology for improving the specificity of SARS-CoV-2 detection without sacrificing sensitivity.
https://www.mdpi.com/2075-4418/10/10/775

As the methodology, they adopted the followings, (1) in the domain of structural protein of SRAS-CoV-2, design dual-target PCR primers targeting on coding region of the accessory and envelope proteins (ORF3ab-E primers) and that of the capsid protein (N primers), and (2) use a peptide nucleic acid (PAN) designed to target on the N region as a blocker of PCR reaction.

Peptide nucleic acids are artificial compounds in which the deoxyribose phosphate backbone is replaced by a pseudo-peptide polymer to which the nucleobases are linked, and the binding affinity for target DNA and RNA is remarkably increased by nearly 1000 times, and therefore, it does not act as a primer but act as an inhibitor of PCR.

As a result, cross-reactivity to other coronaviruses and influenza viruses disappeared completely, and the detection rate of SARS-CoV-2 was 100% for ORF3ab-E and 82.6% for PNA-N.

The S protein of the new coronavirus (SARS-CoV-2) is divided into S1 sites that bind to the host receptors and S2 sites for membrane fusion. The boundary site of this S1 site and S2 site has a furin cleavage site, and there is a target domain of transmembrane protease serine 2 (TMPRSS2) in the S2 site. The following research has been reported that the use of inhibitors on those proteases may be able to reduce the infection of the new coronavirus.
https://linkinghub.elsevier.com/retrieve/pii/S2211-1247(20)31243-2

decanoyl-RVKR-chlorometylketone (CMK) for a furin inhibitor, camostat for a TMPRSS2 inhibitor, as well as naphthofluorescein which inhibits RNA replication, were studied. VeroE6 cells are used for the experiments.

 
Obtained efficacy and toxicity were as follows; the 50% inhibitory concentration (IC50) was 0.057 μM for CMK, 9.025 μM for naphthofluorescein, and 0.025 μM for camostat. The 50% cytotoxic concentration (CC50) was 318.2 μM for CMK, 57.44 μM for naphthofluorescein, and 2,000 μM for camostat. The resulting selection index is 5,567 for CMK, 6.36 for naphthofluorescein, and 81,004 for camostat.

Note that there is a difference among these inhibitors, CMK and camostat prevent the initial infection of the virus, and naphthofluorescein prevents the replication of the virus. We look forward to further consideration as a lead compound for the development of therapeutic drugs in the future.

The Univ. of Nebraska Medical Center group has reported a research finding that bromelain extracted from pineapples (enzyme classified as a cysteine protease in proteolytic enzymes) is effective in suppressing infection with the new coronavirus (SARS-Co-2).
https://www.biorxiv.org/content/10.1101/2020.09.16.297366v1

Bromelain targets angiotensin-converting enzyme 2 (ACE2), type II membrane-penetrating serine protease (TMPRSS2) and SARS-CoV-2 S-protein, and thereby suppresses SAS-CoV-2 infection. Because bromelain is well absorbed through digestive organs and maintains its biochemical activity in the body, it is said that ingesting pineapples rich in bromelain will suppress infection with the new coronavirus (SARS-CoV-2).