Chem 32002 ± Fall 2020: Biochemistry article review

1. General information

Student name & email:

Date submitted:

Article reference (including Author names / Title of article / Source (journal / newspaper / site) / Year /

Volume / Page numbers):

Mitra, A., Ko, Y., Cingolani, G. et al. Heme and hemoglobin utilization by Mycobacterium

tuberculosis. Nat Commun 10, 4260 (2019).

Citation DOI:

2. Summary of article (1500-2000 words):

Mycobacterium tuberculosis (Mtb) is a type of bacteria that is part of the respiratory system which has

a waxy layer because of the mycolic acid present. Majority of the iron that our body stores is found in

heme, which is hydrophobic. Heme has the highest iron source, and it is estimated to have about

70% of the total iron in our body. Iron helps perform a critical function when it comes to taking care of

bacterial infections. There is evidence that shows the high amount of iron can cause a high risk of

Tuberculosis (TB) pathogenesis. Due to gene variation such as haptoglobin, high levels of iron build

up in the blood cell which could lead to an increased risk of TB.

In the event of severe low levels of iron, Mtb secretes siderophores, which are molecules that have

the ability for high iron-binding affinity. It is secreted by bacteria and is used for iron transport through

the cell membrane. It was first proposed that MmpL3 and MmpL11 were responsible for heme

utilization, but it was later found out that they were used as a pump to export lipids as a maintenance

function for the mycobacterial cell wall. It is still unclear whether MmpL3 and MmpL11 do play a role

in the heme utilization by Mtb. It was later discovered that heme-binding proteins present on the cell

surface such as PPE36 and PPE62 were used for heme utilization by Mtb. The study also wanted to

test where PPE36 and PPE62 were responsible for hemoglobin utilization as well. They were placed

in a medium with heme and hemoglobin. Because there was no growth of Δppe36 mutant with heme

or hemoglobin as their only iron source, this tells us that PPE36 is required for both heme and

hemoglobin utilization. Similar results were found for PPE62. When the siderophores deficient mutant

was infected, the survival rate decreased drastically after 72 hours. Based on their study, it showed

that PPE36 was essential for heme utilization and nothing was mentioned about PPE37. But recently

we see that PPE37 is essential and PPE36 is not. The reason for this could be that gene variation

caused changes in the requirements for the Mtb utilization. It was important to note that the study did

not test whether PPE37 played any role in heme and hemoglobin utilization by Mtb.

The study tested whether Dpp transporter plays a part in heme utilization. First, by doing a

homologous recombination, the dpp operon was removed from the Mtb strain. Homologous


Citation: Tsang, N.Y.; Li, W.-F.;

Varhegyi, E.; Rong, L.; Zhang, H.-J.

Ebola Entry Inhibitors Discovered

from Maesa perlarius. Int. J. Mol. Sci.

2022, 23, 2620.


Academic Editor:

Martin Hohenegger

Received: 31 December 2021

Accepted: 23 February 2022

Published: 27 February 2022

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Attribution (CC BY) license (https://


International Journal of

Molecular Sciences


Ebola Entry Inhibitors Discovered from Maesa perlarius
Nga Yi Tsang 1,† , Wan-Fei Li 1,†, Elizabeth Varhegyi 2,† , Lijun Rong 2,* and Hong-Jie Zhang 1,*

1 Teaching and Research Division, School of Chinese Medicine, Hong Kong Baptist University, Kowloon,
Hong Kong, China; [email protected] (N.Y.T.); [email protected] (W.-F.L.)

2 Department of Microbiology and Immunology, College of Medicine, University of Illinois Chicago,
909 South Wolcott Ave, Chicago, IL 60612, USA; [email protected]

* Correspondence: [email protected] (L.R.); [email protected] (H.-J.Z.); Tel.: +1-312-3550203 (L.R.);
+852-34112956 (H.-J.Z.)

† These authors contributed equally to this work.

Abstract: Ebola virus disease (EVD), a disease caused by infection with Ebola virus (EBOV), is
characterized by hemorrhagic fever and a high case fatality rate. With limited options for the
treatment of EVD, anti-Ebola viral therapeutics need to be urgently developed. In this study, over
500 extracts of medicinal plants collected in the Lingnan region were tested against infection with
Ebola-virus-pseudotyped particles (EBOVpp), leading to the discovery of Maesa perlarius as an anti-
EBOV plant lead. The methanol extract (MPBE) of the stems of this plant showed an inhibitory effect
against EBOVpp, with an IC50 value of 0.52 µg/mL, which was confirmed by testing the extract
against infectious EBOV in a biosafety level 4 laboratory. The bioassay-guided fractionation of MPBE
resulted in three proanthocyanidins (procyanidin B2 (1), procyanidin C1 (2), and epicatechin-(4β→8)-
epicatechin-(4β→8)-epicatechin-(4β→8)-epicatechin (3)), along with two flavan-3-ols ((+)-catechin (4)
and (−)-epicatechin (5)). The IC50 values of the compounds against pseudovirion-bearing EBOV-GP
ranged from 0.83 to 36.0 µM, with 1 as the most potent inhibitor. The anti-EBOV activities of five
synthetic derivatives together with six commercially available analogues, including EGCG ((−)-
epigallocatechin-3-O-gallate (8)), were further investigated. Molecular docking analysis and binding
affinity measurement suggested the EBOV glycoprotein could be a potential molecular target for 1
and its related compounds.

Keywords: anti-Ebola virus acti

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