COVID-19 – it’s in the genes

By Mohd Firdaus Raih

There has been no escaping the pervasive imagery of the ball-like shape with appendages that we know as the COVID-19 virus. Although we often refer to both the virus and the disease as COVID-19, the official scientific name for the virus is actually SARS-CoV-2. For us Malaysians, the shape of a single SARS-CoV-2 is rather reminiscent of a rambutan. The virus’ physical shape serves the sole purpose of delivering the genetic payload contained within, referred to as a genome, to the next host. Once inside, the virus hijacks the host cells to make more viruses using the information encoded in the genome.

A genome is the total genetic content of an organism. All livings things have a genome and although viruses are not considered as alive, they too have genomes. The SARS-CoV-2 genome is composed of a chemical substance called RNA. It is very similar to the DNA that we are perhaps more familiar with because the majority of organisms use DNA as the constituents of their genomes. We understand this fact to the extent that we often use the term DNA to refer to any lineage in general. Several viruses such as SARS-CoV-2 and HIV, use RNA and not DNA as their genomic material.

The information encoded within the genome can be extracted by a method called genome sequencing. The process of genome sequencing generates large amounts of data in the form of the letters – A, C, G and T – that are strung along in various combinations. Each letter, is referred to as a nucleotide, and is the basic unit of a genome (nucleotides are also referred to as bases and base pairs; but we’ll not get into those differences here).

The genome of SARS-CoV-2 contains nearly 30,000 nucleotides. Compared to other viruses, it is relatively large. However, compared to many other living organisms, its genome is miniscule – humans have more than 3 billion nucleotides, many bacteria will have millions; even the smallest known genome for a bacteria contains hundreds of thousands nucleotides.

The sequence of these nucleotides in the genome determine the type of proteins that the virus needs to assemble into a complete virus inside the host cell and continue the vicious cycle of infecting the next host. Fit for purpose algorithms and specific software applications running on powerful computers, including supercomputers, process the sequence data in order to decipher the role each protein plays in the life cycle of the virus. This field that utilizes information science and computations to study biological function is called bioinformatics and computational biology.

In general, scientists analyse the genome sequences to identify variations, sometimes termed as mutations. Such information can also be used to track the genetic footprint left behind by the virus as it transmits from host to host. In addition to using the genome as a molecular tracking system, analysis of the variations can also reveal to scientists the potential effects of the mutations towards the virus’ capacity to infect its host and cause disease.

It was the discovery of a specific mutation profile that led scientists to classify the COVID-19 virus as a newly discovered (novel) coronavirus that is distinct from its genetic cousin, the SARS coronavirus. Those particular mutations point to SARS-CoV-2 being more adept at invading the human host and as a consequence perhaps makes it more transmissible than SARS. To date, more than 30,000 SARS-CoV-2 genomes have been sequenced throughout the world. The data from this global effort has been deposited in a database called GISAID – (Global Initiative on Sharing All Influenza Data).

Genome sequences from Malaysia, generated by the Malaysia Genome Institute (MGI), the National Public Health Laboratory (MKAK), the Institute for Medical Research (IMR) and the University of Malaya (UM), have also been added to this global repository. With the currently available data, the viruses isolated in Malaysia can be classified into three lineages or genetically distinct set of virus types – lineage A, B and B.6. There are currently more than 40 lineages that have been determined based on the mutations detected in the genomes.

Genetic mutations are expected. In fact, those variations are a factor that differentiate us as individuals. Mutations do not necessarily lead to sinister outcomes as perhaps often depicted in fiction. SARS-CoV-2 is known to be a relatively slow mutating virus. Despite that, scientists are still keeping a close watch on the evolving virus in order to assess the possibility of future mutations being able to significantly change the virus’ capacity to become deadlier.

Although there is no direct evidence linking any of the observed mutations to the emergence of a more lethal virus, it is clear that some patients are more severely affected by an infection than others. For some individuals, the infection passes through with no symptoms. Yes, it is true many deaths have been in the elderly population, but the GISAID data have revealed that there are also many in their 90s who have survived or have tested positive for COVID-19 despite the lack of symptoms.

This points to the genetics and environmental circumstances of the individual hosts as being crucial factors that determine how each body responds to the infection or is affected by the virus. Therefore, the obvious next course of investigation to understand COVID-19 is to understand what sets all these individuals apart. To do that, scientists would have to gather massive amounts of data that include the genome sequences of individuals who have
succumbed to COVID-19 together with those who have survived and are asymptomatic as comparisons.

But even that will not be enough. Scientists now understand that external and environmental pressures can also exert their influence into how genes behave. As a result, input data regarding personal habits, work and home environment, perhaps even diet, will need to be integrated and analyzed together with the genetics. The use of deep learning or artificial intelligence algorithms can facilitate the discovery of correlations between numerous factors and individual genetic profiles.

Armed with the knowledge of how certain patients can be more susceptible, or can be treated in some specific way, physicians may be able to come up with better and more precise clinical management strategies. Should vaccines or drugs be unavailable in the coming months or years, such an approach would be the best hope of allowing the global healthcare infrastructure to cope and to allow us to live with COVID-19 in our midst.

The writer is a bioinformatician at Universiti Kebangsaan Malaysia and President of the Malaysian Society for Bioinformatics and Computational Biology.


In the year 2020, of revolution and evolution

By Mohd Firdaus Raih

This year, Malaysia was supposed to have achieved its Vision 2020 (Wawasan 2020) goals that were outlined nearly three decades ago. Yet, at half-way through 2020, what we see around us is global scale disruption, hardly the prosperity and progress that we may have expected. The struggle against the COVID-19 pandemic still has no end in sight.

Infections by the SARS-CoV-2 virus has not just taken hundreds of thousands of lives, but it has also dictated and rewritten our way of life. Even as the Movement Control Order (MCO) is lifted in Malaysia, our lives will not be returning to the normal we had left behind in March. After more than two months of MCOs, yet more are still possible. In fact, until a vaccine comes along, moving in and out of MCOs may be a feature of our existence in the years to come.

Given such bleakness, it is unsurprising that we cannot see the glint of any silver lining to look forward to. We may even find it impossible to appreciate that the COVID-19 pandemic is a revolution in progress. It was an event that was merely waiting to happen and perhaps needed to happen to provide the push for us to evolve for a future where pandemics and climate change may force us to provide our planet and our society the time and means to recuperate.

For the past few decades, we have been building up to a point where much of the enablers for a technological revolution are in place. Some may argue that we had already arrived in such an era, referred to as the Industrial Revolution 4.0 (IR4.0). Even so, we may not have fully embraced it. For the past several years, we have been just shy of actually realizing the full potential of all that capacity. We can attribute the lack of uptake or acceptance to various issues including but not limited to mere resistance to change and lacking the economies of scale.

COVID-19 has pushed us to jump those last few hurdles. Passing them is no longer a matter of choice but has become a matter of survival. Earlier in the year, many of us would probably have still been handling cash transactions on an almost daily basis. But today, even the low-tech neighbourhood sundry shop has some form of an online store in addition to accepting electronic or non-cash payments.

Consumer volume and acceptance are no longer the limitations or an excuse. Service providers can no longer refrain from committing capital investments by citing lack of traffic volume. The surge of online content consumers from all age groups and diverse socio-economic backgrounds means that access to online content has permeated through society. This culture change in the consumption of content and services delivered via the internet will hopefully also spur revolutions in the overstretched supply chain and logistics sectors.

Online education technology has existed for some time. But let’s face it, online teaching has not been the preferred mode of delivering mainstream education content. As a result, despite numerous efforts to make online education more extensive, that potential was never fully realized until the present situation warranted no other alternatives. The same can be said of other sectors where feet-dragging and bureaucracy have hidden behind the labels of quality control measures for many years. This current situation of travel limitations and fuel price instability will also force industries such as commercial aviation to adapt, innovate and evolve. To borrow a phrase from Star Trek – resistance is futile.

As in other sectors mentioned, COVID-19 has also pushed the cutting-edge envelope in medical and scientific research. The amount and pace of research being carried out on COVID-19 and the SARS-CoV-2 virus are unprecedented. This has led to the prospect of vaccines being possible as early as later this year. To put that time-frame into context, an Ebola vaccine has taken some five years of development after decades of research, while a vaccine for HIV has not come to fruition despite the virus being studied for almost 40 years.

COVID-19 has also accelerated the notoriously slow process of drug research. An approach called drug repurposing, previously not favoured by some quarters because it was deemed to be less profitable, is now the go to solution to provide drug intervention options for COVID-19 treatment. By using drugs already approved for human use, drug repurposing can bypass the decades long process of developing and approving a new drug. The dire circumstances of the current situation no longer allow for selfishness and negativity. Resisting to expel such attitudes from within ourselves will result in us being left behind. Collaboration and openness are a necessity in an age when individual interactions need to be distanced and covered up.

The year 2020 also marks the coming of age of an idea that began more than five decades ago, when a group of nationalists mooted the concept of a university that used the Malay language as a medium of instruction. This led to the establishment of a national university for Malaysia – Universiti Kebangsaan Malaysia (UKM). Its role as a national university has evolved beyond just championing the Malay world and employing the Malay language as the medium of instruction.

As a national university, UKM must not only undertake a role as the custodian of national heritage, but must also pave the way to lead Malaysia into the future. This national duty will be served by being an incubator to nurture possibilities that will in turn lead to inspirational research, and also by educating the next generation of Malaysian leaders and patriots who will lead not only our nation, but also have principal roles on the global stage.

A university is generally considered as reaching maturity upon its 50th year. For UKM, the date of the golden jubilee was reached on the 18th of May 2020. There can be no better accolade and testament to the success of a university than its alumni. In the backdrop of this pandemic, UKM alumni have become the public faces for the response and management of the pandemic, in addition to various critical roles in keeping the country going.

The expectations of those who mooted for the establishment of a national university went beyond merely providing accessible tertiary education for providing manpower to the civil service. While many alumni have indeed assumed key positions in government, many others have taken roles that are perhaps more unexpected for graduates of a university with instruction in the Malay language. Among those roles include leadership of an English language media group and various respectable positions in many overseas institutions. Having a university degree instructed in Malay has not proven to be a handicap or negative factor.

Disruptive global events such as world wars and pandemics are obviously never welcomed. However, the resulting adversity will force us to innovate, adapt, and to evolve beyond the normal reference points. In the process, we must preserve the essence of our traditions, ethics and morals but practice them via new manifestations and evolve a new culture. For us to remain relevant, we must initiate a revolution from within to reinvent ourselves. Our very survival as a nation and perhaps as the human race as we know now depends on it.

The founders of UKM may not have imagined that as the realization of their dreams reached 50 years of age, universities, especially a national university, will again need to dig deep to reinvent themselves to meet novel challenges. In the coming months, universities must undertake a leading and crucial role in facilitating and engineering how we respond as a nation and as a society in adapting to the new normal.

*The writer is a bioinformatician at Universiti Kebangsaan Malaysia and President of the MaSBiC.


Keharmonian kerajaan, saintis bendung COVID-19

Segerakan ujian saringan antara langkah awal membendung penularan wabak COVID-19. – NSTP/Aswadi Alias

Oleh Prof Madya Dr Tengku Haziyamin Tengku Abdul Hamid

KETIKA wabak COVID-19, banyak negara mengalami fasa perintah berkurung atau Perintah Kawalan Pergerakan (PKP) sebagai langkah membendung penyebaran.

Walaupun PKP menjejaskan banyak kehidupan, keselamatan rakyat menjadi isu utama jika wabak sudah tersebar.

Cabaran pemimpin sesebuah negara adalah ketika membuat keputusan sama ada mendahulukan kepentingan ekonomi atau keselamatan rakyat.

Sebarang bentuk kesilapan akan mengakibatkan kebanjiran pesakit di institusi kesihatan yang kelengkapan dan kakitangannya mungkin terhad.

Keharmonian terbentuk antara pemimpin politik dengan saintis amat penting dalam menentukan tindak balas sesebuah negara ketika krisis pandemik.

Misalnya, Kerajaan China dikatakan cuba untuk menafikan kewujudan coronavirus baharu yang mula disedari di Wuhan.

Sememangnya dari awal lagi, dikatakan sudah wujud semacam amaran saintis di China mengenai virus ini. Akhirnya kerajaan terpaksa akur dan sekarang COVID-19 menjadi pandemik.

Di Amerika Syarikat (AS) pula, Presiden Donald Trump begitu tegas mengumumkan pengurangan dana penyelidikan sains dan sumbangan kepada Pertubuhan Kesihatan Sedunia (WHO).

Tindakan Trump dilihat sebahagian langkah politiknya untuk mengembalikan ‘kegemilangan’ AS. Trump dilihat menganggap ringan pandangan pakar penyakit berjangkit, Dr Anthony Fauci.

Trump seolah memperkecilkan COVID-19 dan secara kontroversi menggelarnya ‘virus China’. Dinamika hubungan Trump-Dr Fauci menjadi genting, terutama di ambang COVID-19 melanda AS.

Sekarang, AS merekodkan sejuta jangkitan dengan lebihi 60,000 kematian.

Di Korea Selatan, satu-satunya negara yang menjadi pusat tular pertama COVID-19 di luar China, Presiden Moon Jae-in dikatakan berjaya membendung wabak itu.

Kunci utama dalam mengawal pandemik ini adalah kemampuan menyaring mereka yang asimtomatik. Tanpa melalui fasa PKP, Korea Selatan melakukan hampir 350,000 saringan dan ini dibantu infrastruktur serta pembangunan sains negara itu yang kukuh.

Korea Selatan membelanjakan kira-kira 5 peratus daripada Keluaran Dalam Negara Kasar (KDNK) dalam sektor penyelidikan dan pembangunan (R&D), sekali gus melebihi AS yang mencatatkan 2.7 peratus dan China (2 peratus).

Di samping itu, kerajaannya dikatakan bertindak secara telus dan berkongsi segala fakta pandemik kepada orang awam.

Di Eropah, Jerman juga dikatakan begitu berjaya dalam mengekang penularan COVID-19. Tatkala negara Eropah lain berdepan dengan situasi darurat, Jerman merekodkan jumlah kematian yang agak kecil.

Dengan jumlah jangkitan melebihi 159,000 orang, Jerman melakukan saringan secara skala besar. Canselor Jerman, Angela Merkel dilihat begitu berjaya dalam mengendalikan COVID-19.

Ia turut dikaitkan dengan latar belakangnya dalam bidang kimia kuantum dan sentiasa terbuka terhadap pandangan saintis Jerman dari semasa ke semasa.

Di New Zealand, Perdana Menteri, Jacinda Ardern mengumumkan negara itu berjaya membendung COVID-19 sepenuhnya pada 27 April lalu.

Dalam kalangan pemimpin Barat, Ardern dilihat berjaya menonjolkan ciri kepemimpinan yang proaktif dengan mengambil berat setiap pandangan saintis, pakar mahupun rakyat.

Pandemik ini menunjukkan ketelusan kerajaan amat penting. Sebagai contoh, Indonesia dengan lebih 250 juta orang penduduk mempunyai jumlah kematian tertinggi di Asia tenggara.

Pada awalnya, kadar jangkitan dilihat agak rendah berbanding Malaysia, Singapura atau Filipina. Sehinggakan WHO kurang yakin dengan angka yang dilaporkan pihak Indonesia.

Pakar tempatan juga mendesak agar kerajaan Jokowi bertindak lebih telus. Pihak kerajaan dikatakan bertindak lewat dan mula memesan kit ujian saringan. Kita tidak pasti jika senario yang sama berlaku di berapa negara di Asia Selatan yang lain.

Apa yang terjadi di beberapa negara menunjukkan kejayaan membendung pandemik bukan sahaja terletak pada infrastruktur canggih dan kemajuan sesebuah negara, ia juga bergantung kepada keharmonian hubungan antara pucuk pimpinan dengan saintis atau pakar.

Di Malaysia, kita menyaksikan COVID-19 hampir berjaya dikawal ke tahap 6,000 jangkitan dengan 100 jumlah kematian.

Kita berharap, bertolak daripada COVID-19, kerjasama dan persefahaman yang wujud antara pemimpin politik dengan pakar kesihatan atau sains menjadi satu budaya yang berterusan dan keupayaan sains negara dapat dipertingkatkan untuk menghadapi sebarang pandemik pada masa akan datang.

Penulis adalah Pensyarah Jabatan Bioteknologi, Kulliyyah Sains, Universiti Islam Antarabangsa Malaysia (UIAM)

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