B38-CAP / Kafrelsheikh University - LARVOL DELTA

Integrated computational approach towards identification of HSPG and ACE2 mimicking moieties for SARS-CoV-2 inhibition. (PubMed, J Mol Liq) - "B38-derived carboxypeptidase (B38-CAP) and Bacillus subtilis-derived carboxypeptidase (BS-CAP) as the potential ACE2-like enzymes having a strong binding affinity to the spike proteins as that of cellular HSPG and ACE2. Further, the binding stability and compactness of these moieties with SARS-CoV-2 were analyzed through molecular dynamics (MD) simulations, and the results indicated that these moieties form well-stable complexes with the RBD of spike proteins. The identified moieties could be conjugated to the surfaces of non-toxic nanoparticles to provide multiple interactions to efficiently shield SARS-CoV-2, and inhibit viral entry to the host cells."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

ACE2-like enzyme B38-CAP suppresses abdominal sepsis and severe acute lung injury. (PubMed, PLoS One) - "B38-CAP suppressed the pathologies of lung inflammation, improved lung dysfunction and downregulated elevated cytokine mRNA levels in the mice with acute lung injury. Thus, systemic treatment with an ACE2-like enzyme might be a potential therapeutic strategy for the patients with severe sepsis or ARDS."

Journal • Acute Lung Injury • Acute Respiratory Distress Syndrome • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Septic Shock • ANGPT1

Structural insights revealed by crystal structure of B38-CAP, an isoenzyme of carboxypeptidase ACE2, the receptor of SARS-CoV-2. (PubMed, Biochem Biophys Res Commun) - "Further structural analysis revealed the structural conservatism feature among M32 family, particularly the catalytic core and moreover lead us to hypothesize that conformational flexibility might play an pivotal role in the catalysis of B38-CAP and ACE2. The work provided here presents key features of the M32 family carboxypeptidase and provides structural basis for further development of B38-CAP-based anti-SARS-CoV-2 drugs."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury. (PubMed, Nat Commun) - "In SARS-CoV-2-infected hamsters or human ACE2 transgenic mice, B38-CAP significantly improves lung edema and pathologies of lung injury. These results provide the first in vivo evidence that increasing ACE2-like enzymatic activity is a potential therapeutic strategy to alleviate lung pathologies in COVID-19 patients."

Journal • Acute Lung Injury • Cardiovascular • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Recombinant Bacterial ACE2 Receptors -Like Enzyme of B38-CAP Could be Promising Treatment for COVID-19 Infection- and Its Inflammatory Complications Better Than Recombinant Human ACE2 (clinicaltrials.gov) - P1; N=24; Not yet recruiting; Sponsor: Kafrelsheikh University; Trial completion date: Jun 2021 ➔ Oct 2021; Trial primary completion date: May 2021 ➔ Aug 2021

Trial completion date • Trial primary completion date • Congestive Heart Failure • Infectious Disease • Novel Coronavirus Disease • ANGPT1 • CRP • CXCL8 • IL6 • PAI1 • TNFA • TNFRSF1B

Combination of Recombinant Bacterial ACE2 Receptors -Like Enzyme of B38-CAP and Isotretinoin Could be Promising Treatment for COVID-19 Infection- and Its Inflammatory Complications (clinicaltrials.gov) - P1; N=24; Not yet recruiting; Sponsor: Kafrelsheikh University; Trial completion date: Dec 2020 ➔ Oct 2021; Trial primary completion date: Nov 2020 ➔ Aug 2021

Trial completion date • Trial primary completion date • Congestive Heart Failure • Infectious Disease • Novel Coronavirus Disease • ANGPT1 • CRP • IL6 • PAI1 • TNFA • TNFRSF1B

Recombinant Bacterial ACE2 Receptors -Like Enzyme of B38-CAP Could be Promising COVID-19 Infection- and Lung Injury Preventing Drug Better Than Recombinant Human ACE2 (clinicaltrials.gov) - P1; N=24; Not yet recruiting; Sponsor: Kafrelsheikh University; Trial completion date: Oct 2020 ➔ Jun 2021; Initiation date: Sep 2020 ➔ Apr 2021; Trial primary completion date: Sep 2020 ➔ May 2021

Trial completion date • Trial initiation date • Trial primary completion date • Congestive Heart Failure • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • ANGPT1 • CRP • CXCL8 • IL6 • PAI1 • TNFA • TNFRSF1B

Combination of Recombinant Bacterial ACE2 Receptors -Like Enzyme of B38-CAP and Isotretinoin Could be Promising COVID-19 Infection- and Lung Injury Preventing Drug Better Than Recombinant Human ACE2 (clinicaltrials.gov) - P1; N=24; Not yet recruiting; Sponsor: Kafrelsheikh University; Trial completion date: Sep 2020 ➔ Dec 2020; Trial primary completion date: Jul 2020 ➔ Nov 2020

Trial completion date • Trial primary completion date • Congestive Heart Failure • Infectious Disease • Novel Coronavirus Disease • Ophthalmology • ANGPT1 • CRP • IL6 • PAI1 • TNFA • TNFRSF1B

Combination of Recombinant Bacterial ACE2 Receptors -Like Enzyme of B38-CAP and Isotretinoin Could be Promising COVID-19 Infection- and Lung Injury Preventing Drug Better Than Recombinant Human ACE2 (clinicaltrials.gov) - P1; N=24; Not yet recruiting; Sponsor: Kafrelsheikh University

New P1 trial • Cardiovascular • Congestive Heart Failure • Heart Failure • Infectious Disease • Novel Coronavirus Disease • Ophthalmology • ANGPT1 • CRP • IL6 • PAI1 (Plasminogen Activator Inhibitor 1) • TNFA • TNFRSF1B

Recombinant Bacterial ACE2 Receptors -Like Enzyme of B38-CAP Could be Promising COVID-19 Infection- and Lung Injury Preventing Drug Better Than Recombinant Human ACE2 (clinicaltrials.gov) - P1; N=24; Not yet recruiting; Sponsor: Kafrelsheikh University

Clinical • New P1 trial • Cardiovascular • Congestive Heart Failure • Heart Failure • Infectious Disease • Novel Coronavirus Disease