Sains Malaysiana 50(4)(2021): 1175-1186

http://doi.org/10.17576/jsm-2021-5004-27

COVID-19 Mini-Review: D614G Mutation as an Independent Risk-Factor to the Expression of ACE2 and DPP4 Associated Increased Severity in COVID-19

(Ulasan Mini COVID-19: Mutasi D614G sebagai Faktor Risiko Bebas kepada Ekspresi ACE2 dan DPP4 Berkait dengan Peningkatan Keparahan COVID-19)

SITI ASMAA MAT JUSOH^1,2, PARISA FOROOZANDEH¹, LEE YAN FEN^1,3, MARDANI ABDUL HALIM^1,4, MANOJ KUMAR LASKMANAN^1,4 & SHAHARUM SHAMSUDDIN^1,2,5*

¹Universiti Sains Malaysia (USM)-RIKEN, Interdisciplinary Collaboration for Advanced Sciences (URICAS), 11700 Gelugor, Pulau Pinang, Malaysia

²School of Health Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan Darul Naim, Malaysia

³School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11700 Gelugor, Pulau Pinang, Malaysia

⁴School of Biological Sciences, Universiti Sains Malaysia, 11700 Gelugor, Pulau Pinang, Malaysia

⁵Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan Darul Naim, Malaysia

Received: 25 November 2020/Accepted: 5 February 2021

ABSTRACT

The novel coronavirus 2019 (COVID-19) has struck more than 99 million people worldwide and had claimed more than 2 million lives as of 23 January 2021, which affecting 221 countries/nations. Until now, the pandemic has not shown signals of slowing down, with no proven vaccine in sight. People are speculating on this unprecedented event. It is well documented that the receptor-binding domain (RBD) of the viral spiked S1 glycoprotein directly bind angiotensin-converting enzyme 2 (ACE2) and dipeptidyl-peptidase-4 (DPP4) or CD26 (cluster of differentiation 26) receptors lead to their entry. The latest evidence demonstrated that SAR-CoV-2 possesses genetic heterogeneity, lead to the existence of a new SAR-CoV-2 variant, such as D614G encoded the spiked S1. The mutation involved changes in amino acid sequence of D (aspartic acid) into G (guanine) at position 614. D614G was reported to confer high infectivity and became the dominant form of the virus globally. Interestingly, current evidence found that D614G protein increases its infectivity dependent on the ACE2 receptor, and its co-binding receptor, DPP4. This proclaims implied to COVID-19 high-risk groups; the aging population and the people with comorbidities; hypertension, cardiovascular disease, and diabetes, which constituted the most of lethal cases, that overexpressed ACE2 and DPP4. The review aims to find an association between COVID-19 infectivity and severity relating to D614G mutation with the expression of ACE2 or DPP4 in these groups. We proposed that D614G mutation and expressions of ACE2 and DPP4 were mutually inclusive for increase infectivity, but not severity in COVID-19’s patients.

Keywords: Angiotensin-converting enzyme 2 (ACE2); COVID-19; dipeptidyl-peptidase-4 (DPP4); D614G mutation 

ABSTRAK

Koronavirus baru 2019 (COVID-19) telah menyerang lebih daripada 99 juta orang di seluruh dunia dan telah meragut lebih daripada 2 juta nyawa sehingga 23 Januari 2021, yang mempengaruhi 221 negara. Hingga kini, wabak ini tidak menunjukkan tanda-tanda pengurangan tanpa vaksin yang terbukti berkesan. Orang ramai membuat spekulasi mengenai peristiwa yang belum pernah terjadi sebelum ini. Didokumentasikan dengan baik bahawa domain pengikat reseptor (RBD) virus, glikoprotein spiked S atau S1 secara langsung mengikat enzim angiotensin-penukar (ACE2) dan dipeptidil-peptidase-4 (DPP4) atau reseptor CD26 (kelompok pembezaan 26) membawa kepada kemasukan mereka. Bukti terbaru menunjukkan bahawa SARCoV-2 memiliki heterogen genetik, menyebabkan wujudnya varian SAR-CoV-2 baru, seperti D614G yang mengekodkan glikoprotein S1. Mutasi tersebut melibatkan perubahan dalam urutan asid amino D (asid aspartik) menjadi G (guanin) pada kedudukan 614. D614G dilaporkan memberikan kebolehjangkitan tinggi dan menjadi bentuk virus yang dominan pada peringkat global. Menariknya, bukti semasa mendapati bahawa protein D614G meningkatkan kebolehjangkitannya bergantung pada reseptor ACE2 dan reseptor pengikat bersama DPP4. Ini merujuk kepada kumpulan berisiko tinggi COVID-19; populasi penuaan dan orang yang mempunyai kokemorbidan; hipertensi, penyakit kardiovaskular dan diabetes, yang merupakan sebahagian besar daripada kes kematian, yang tinggi ekspresi ACE2 dan DPP4. Ulasan ini bertujuan untuk mencari hubungan antara kebolehjangkitan dan keparahan COVID-19 yang berkaitan dengan mutasi D614G dengan ekspresi ACE2 atau DPP4 dalam kumpulan ini. Kami mencadangkan bahawa mutasi D614G dan ekspresi ACE2 dan DPP4 saling inklusif untuk meningkatkan kebolehjangkitan, tetapi tidak keparahan pada pesakit COVID-19.

Kata kunci: COVID-19; dipeptidil-peptidase-4 (DPP4); enzim angiotensin-penukar 2 (ACE2); mutasi D614G

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*Corresponding author; email: shaharum1@usm.my