Replicationprocess

Cell membrane

Viral protein

TMPRSS2

Protein-makingmachinery

ACE2

NewSars-CoV-2

Sars-CoV-2

Spike protein on the virus binds to ACE2, a cell-surface protein. Enzyme TMPRSS2 helps the virus enter

Some RNA is translated into proteins by the cell’s machinery

Some of these proteins form a replication complex to make more RNA

Proteins and RNA are assembled into a new virus

New virus is created

The virus releases its RNA

1 2 3 4 5

How Sars-CoV-2 replicates

MODUS OPERANDI

Last December, an unknown virus surfaced at a market in Wuhan, China. It has since exploded worldwide, thwarting efforts to contain it. A silent assassin, the virus is still shrouded in mystery. Doctors and scientists — the detectives of the microbial world — have uncovered some answers and are racing to develop an accurate pro�le. AUDREY TAN and TIMOTHY GOH highlight the twists, turns and missteps in the �ght against Covid-19, as the world strives to keep up with its tricks.

DETECTIONIn an outbreak of an infectious disease like Covid-19, diagnosing patients is a key �rst step to preventing its spread.

Polymerase chain reaction (PCR) testsThis method, which makes use of a process known as PCR, is considered the "goldstandard" method as it can detect small amounts of viral genetic material in patient samples. This PCR technique ampli�es the genetic material of the virus so that it can be easily detected and analysed. But it is time-consuming and technical, since it involves expensive machinery that also requires trained technicians to operate. Turnaround time for results could take up to a day.

Rapid diagnostic testsThese tests allow speedy diagnosis to be done, with some designed to be as fuss-free as a pregnancy test.These point-of-care test kits do not require specimens to be sent to laboratories, unlike PCR tests. These tests are still a work in progress.

Serology testsThese tests detect the presence of antibodies produced by the immune system against the virus.Patients have antibodies around two weeks after they recover from the infection and will not have them at the point of infection. It remains inconclusive whether antibodies are always protective, or how long immune memory would last against Covid-19.

ELIMINATIONVaccines• Vaccines are a preventive strategy that could inoculate the vast majority of the population before they get infected.• Local company Esco Aster is working on a “chimeric vaccine” in collaboration with Vivaldi Biosciences. Made by joining antigens from the Sars-CoV-2 virus with a protein “backbone” from the �u virus, the vaccine will be able to grant immunity from Covid-19 and the �u. • Duke-NUS is working on an mRNA vaccine in collaboration with Arcturus Therapeutics. The vaccine works by injecting part of the virus’ genetic material into the patient’s body, which then makes the part of the virus that its immune response needs to recognise and generate memory against. This allows the immune system to “recognise” the virus, kick-starting the production of antibodies, without actually exposing the patient to the risk of infection.

Antibody therapy• Antibodies, which are found in the blood, are an important part of the immune system. They latch on to infected cells and “�ag” them to the rest of the immune system, allowing it to begin destroying the disease.• Lab-grown antibodies are injected into the patient’s bloodstream, serving as substitute antibodies.• The Agency for Science, Technology and Research is collaborating with Chugai Pharmabody Research on a therapeutic antibody to �ght Covid-19. It works by binding itself to the crown of the virus, preventing it from attaching itself to human cells.

Biography

Name: Sars-CoV-2This virus is in the same family as the one that caused the outbreak of the severe acute respiratory syndrome (Sars) in 2003.

Disease caused: Covid-19Symptoms: Mainly fever, dry cough and tiredness. Less common symptoms include aches, nasal congestion, headache, conjunctivitis, sore throat, diarrhoea, loss of taste or smell, or a rash on skin or discoloration of �ngers or toes.

Lives claimed: About 300,000

What is a genome?• The RNA of the virus is made up of an “alphabet” of molecules known as nucleotides. It has four different nucleotide bases that function as the basic building blocks – adenine (a), cytosine (c), guanine (g) and uracil (u).• The way in which these four nucleotide bases are arranged is unique to the speci�c virus, similar to how human �ngerprints can help to differentiate one person from another.

DisguisesAll viruses are prone to mutation, and Sars-CoV-2 is no exception. But whether it has mutated in a way that helps it spread faster or makes it more deadly is the subject of ongoing research.

What is a mutation?• The genome of the virus causing Covid-19 has about 30,000 “letters” in all. In comparison, the human genome is about three billion “letters” long. • Mutation occurs when the virus copies itself but makes typos in the process, causing some letters in some positions to be exchanged. For example, when a is swopped with c at position 24073, it is called an A24073C mutation.

December 2019• A string of pneumonia-like cases surfaces in Wuhan, China.

January 2020• Chinese scientists upload the full genome of Sars-CoV-2 - the virus which causes Covid-19, onto a public database. Scientists now know it is closely related to the Sars virus.

• China reports human-to-human transmission of the virus.

• Reports say China is using HIV drugs to

The RNA is made up ofnucleotides

Spike glycoprotein

TIMELINE

Sources: THE ECONOMIST, NATURE, ST FILE, WORLD HEALTH ORGANISATION, A*STAR PHOTO: AFP STRAITS TIMES GRAPHICS

treat some patients.• Research teams begin work on vaccines.

February 2020• The National Centre for Infectious Diseases (NCID) says there is no robust proof that the coronavirus can be spread by someone with no symptoms.

• A diagnostic test kit developed by the Agency for Science, Technology and Research (A*Star) and Tan Tock Seng Hospital is rolled out at local institutions.

• Singapore scientists say they are working with international partners to develop a trial for a vaccine for the coronavirus, with plans to begin testing it in as soon as four months.

March 2020 • The World Health Organisation declares Covid-19 a pandemic, citing alarming levels of spread globally.

• The global health body also launches Solidarity, a large global trial involving at least 10 countries, to simultaneously test

four promising treatments against the disease.

• A paper suggests two types of the coronavirus — L and S types — appear to exist, with the L type being more aggressive and spreading more quickly than the other. The claims are debunked by other scientists. As the disease spreads, so too does unreliable science and fake news.

• A*Star scientists discover a potential therapeutic antibody which targets the “crown” of the virus

that latches onto the human cell.

April 2020 • A*Star con�rms the antibody it discovered earlier in March can prevent infection.

• NCID says asymptomatic people with Covid-19 are more common than previously thought, and that they could be infecting people without anyone �nding out. Wearing a mask when leaving home is made mandatory.

• Studies �nd that men are more likely to

die from the virus, and that in some countries, certain races, including African Americans and Asians, may be more likely to die from the disease. Reasons for this are not clear, but could be due to genetic or behavioural differences.

• Scientists from Oxford University race ahead in the quest for a promising vaccine, with the �rst few million doses estimated to be available by September, months ahead of anyone else.

• Around 70 potential vaccines are being tested. American drug makers like Moderna also have vaccine candidates in human trials, as do researchers from Oxford University. Chinese scientists have at least three others in human trials.

May 2020• Scientists publish a paper in Nature suggesting that the coronavirus could have originated as a blend of pangolin and bat

corona-like viruses. Discovering the animal hosts of the virus is important as it could allow action to be taken to reduce the exposure of humans to the animal. It could also help scientists understand how the virus adapted to be able to infect humans.

• The Ebola drug remdesivir appears to

be the most promising drug to date, speeding up recovery times for patients with Covid-19 in a major US-led trial, becoming the �rst drug with proven bene�tagainst the disease.

Coronavirus pandemic

| THURSDAY, MAY 14, 2020 | THE STRAITS TIMES | TOPOFTHENEWS A7